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  • American Society of Hematology  (96)
  • 2020-2024  (96)
  • 1
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 45-49
    Abstract: Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020; Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects. Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts. CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. & lt;6), CLL treatment history, details regarding COVID-19 course, management, and therapy, and vital status were collected. The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies; univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx). Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98); 31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2). Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L; 27% vs. 21%), and lymphocytopenia (ALC & lt; 1.0 x 109/L; 18% vs. 28%), while others varied between Co1 and Co2 (p & lt;0.0001), including cough (61% vs. 93%), dyspnea (60% vs. 84%), fatigue (13% vs. 77%). Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p & lt;0.0001). Figure 1 depicts OS in each cohort. Univariable analyses demonstrated that age and CIRS ≥6 significantly predicted inferior OS in both cohorts, while only age remained an independent predictor of inferior OS in multivariable analyses (Table 2). Prior treatment for CLL (vs. observation) predicted inferior OS in Co1 but not Co2. Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including therapeutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts; COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented. Disclosures Roeker: American Society of Hematology: Research Funding; Abbott Laboratories: Other: spouse with minority ownership interest ; AbbVie: Other: spouse with minority ownership interest . Scarfo:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. Eyre:AbbVie: Consultancy, Honoraria, Other: travel support; Gilead: Consultancy, Honoraria, Other: travel support; Janssen: Consultancy, Honoraria, Other: travel support; KITE, AZ, Loxo Oncology at Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Muntañola Prat:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards. Villacampa:AstraZeneca: Other: advisory role; Merck Sharp & Dohme: Honoraria. Leslie:AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Speakers Bureau; Karyopharm: Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Allan:Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy; Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria. Furman:Incyte: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Pharmacyclics: Consultancy; Loxo Oncology: Consultancy; Oncotarget: Consultancy; Janssen: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Verastem: Consultancy. Pagel:BeiGene, Astrazeneca, Loxo Oncology, Gilead: Consultancy. Hernandez-Rivas:Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Patel:Genentech: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy; Janssen: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Motta:Roche: Honoraria; Janssen: Honoraria. Lamanna:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Verastem: Research Funding; Bei-Gene: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Vitale:Janssen: Honoraria. Kamdar:Roche: Research Funding. Österborg:BeiGene: Research Funding; Kancera: Current equity holder in publicly-traded company, Research Funding; Sanofi: Consultancy; Karolinska Univeristy Hospital, Stockholm, Sweden: Current Employment. Hanson:Janssen-Cilag: Research Funding; Gilead: Research Funding; AbbVie: Honoraria. Eichhorst:ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding. Reda:Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Varettoni:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses; AbbVie: Other: Travel/accommodations/expenses; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees. Marchetti:Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Other: Sponsored meetings; Takeda: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings. Munir:F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland; Alexion: Honoraria. Zabalza:Janssen: Honoraria, Other: travel grants; Roche: Other: travel grants; Novartis: Other: travel grants. Janssens:Amgen: Consultancy, Other: travel grants; speaker fees; Abbvie: Consultancy, Other: travel grants; speaker fees; Celgene: Consultancy, Other: travel grants; speaker fees; Janssen: Consultancy, Other: travel grants; speaker fees; Gilead: Consultancy, Other: travel grants; speaker fees; Novartis: Consultancy, Other: travel grants; speaker fees; Sanofi-Genzyme: Consultancy, Other: travel grants; speaker fees; Roche: Consultancy, Other: travel grants; speaker fees. Niemann:AstraZeneca: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Sunesis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Danish Cancer Society: Honoraria, Research Funding; Novo Nordisk Foundation: Honoraria, Research Funding. Perini:Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Abbvie: Speakers Bureau. Patten:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Honoraria. Marasca:Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Honoraria. Iyengar:Janssen: Honoraria; Gilead: Honoraria. Ferrari:Abbvie: Honoraria. El-Sharkawi:Roche: Other: Conference fees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Itchaki:Abbvie Inc: Consultancy, Research Funding. Ma:Novartis: Research Funding; Juno: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Bioverativ: Consultancy, Honoraria; BeiGene: Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; TG Therapeutics: Research Funding. Van Der Spek:AMGEN: Other: Teaching activities. Seymour:Seattle Genetics: Research Funding; Merck: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding. Rigolin:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mauro:Roche: Other; Octopharma: Other; Takeda-Shire: Other; Gilead: Other; Janssen: Other; Abbvie: Other. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Levin:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation. Špaček:Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Walewska:AbbVie: Other: sponsored for educational meetings, Speakers Bureau; Janssen: Other: sponsored for educational meetings, Speakers Bureau; Gilead: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Wiestner:Pharmacyclics LLC, an AbbVie Company; Acerta, Merck, Nurix, Verastem, and Genmab: Research Funding; National Institutes of Health: Patents & Royalties: and other intellectual property. Broom:Gilead: Other: Travel support, Speakers Bureau. Kater:Abbvie: Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Genentech: Research Funding. Ujjani:AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Verastem Oncology: Consultancy, Honoraria; Gilead/Kite: Consultancy, Research Funding; Atara: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; MorphoSys: Consultancy. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Gilead: Other: travel grants, Research Funding; Abbvie: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Chong:Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; KITE Pharma: Membership on an entity's Board of Directors or advisory committees. Pu:Takeda Pharmaceuticals: Consultancy. Brown:Janssen, Teva: Speakers Bureau; Gilead, Loxo, Sun, Verastem: Research Funding; Abbvie, Acerta, AstraZeneca, Beigene, Invectys, Juno/Celgene, Kite, Morphosys, Novartis, Octapharma, Pharmacyclics, Sunesis, TG Therapeutics, Verastem: Consultancy. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Sanchez:Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Shadman:Abbvie, Genentech, Astra Zeneca, Sound Biologics , Pharmacyclics, Verastem, ADC therapeutics, Beigene, Cellectar, BMS, Morphosys and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Pharmacyclics, Gilead, Genentech, Abbvie, TG therapeutics, Beigene, Astra Zeneca, Sunesis, Beigene: Research Funding. Foglietta:Janssen: Honoraria; Gilead: Honoraria. Jaksic:Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Sportoletti:AbbVie: Honoraria; Janssen: Honoraria. Barr:Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Verastem: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy; Merck: Consultancy; Genentech: Consultancy; Janssen: Consultancy. Ruchlemer:Abbvie Inc: Consultancy, Research Funding. Kersting:Celgene: Other: travel grant; Janssen: Research Funding; Abbvie: Research Funding. Huntington:Pharmacyclics: Honoraria; AbbVie: Consultancy; Novartis: Consultancy; Genentech: Consultancy; DTRM: Research Funding; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; TG Therapeutics: Research Funding. Herishanu:Roche: Honoraria; Sanofi: Honoraria; Medison: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria. Jacobs:TG Therapeutics, Inc.: Research Funding; Astra Zeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; Seattle Genetics: Consultancy; Verastem: Consultancy; Janssen: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Sanofi Genzyme: Speakers Bureau. Portell:BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding; Bayer: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; AbbVie: Research Funding. Rambaldi:Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Astellas: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); University of Milan: Current Employment; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Received travel support., Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support from Gilead.; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Research grant from Amgen Inc.; Omeros: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Advisory board and speaker fees from Pfizer.. Brander:Verastem: Consultancy, Honoraria, Other, Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding. Rossi:Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Coscia:Karyopharm Therapeutics: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Coombs:Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; MEI Pharma: Honoraria; LOXO Oncology: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. Schuster:Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria. Foà:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cuneo:Astra Zeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bosch:Jansen: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Astra Zeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Roche: Honoraria. Stamatopoulos:AstraZeneca: Honoraria; Janssen, Gilead, Abbvie: Honoraria, Research Funding. Ghia:Adaptive, Dynamo: Consultancy, Honoraria; Novartis: Research Funding; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene/Juno: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; MEI: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Research Funding; ArQule: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria. Mato:Adaptive: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 2 ( 2021-12-04), p. LBA-6-LBA-6
    Abstract: Background: Standard of care (SOC) for second-line (2L) therapy (tx) of relapsed/refractory aggressive B-cell non-Hodgkin lymphomas (R/R aNHL) includes platinum-based chemotherapy (PCT) followed by autologous hematopoietic cell transplantation (aHCT) in responders. Outcomes are poor for patients (pts) with R/R aNHL who experience progression during or within 12 months (mo) of 1L tx. Tisagenlecleucel (tisa-cel) is an autologous chimeric antigen receptor (CAR) T-cell tx targeting CD19 approved for pts with large B-cell lymphoma (LBCL; US) and diffuse LBCL (non-US) after ≥2 lines of tx. BELINDA (NCT03570892) is a Phase III, randomized, global (18 countries) study of tisa-cel vs SOC as 2L tx for R/R aNHL. Methods: Adults with confirmed R/R aNHL within 12 mo after 1L chemo-immunotherapy were eligible. All pts underwent leukapheresis for tisa-cel production and were randomized 1:1 to receive tisa-cel (Arm A) or SOC (Arm B) and stratified by 1L duration of response, International Prognostic Index (IPI), and geographic region. Arm A received optional bridging tx (investigator choice of protocol-defined PCT regimens) followed by lymphodepletion (LD; generally, fludarabine 25 mg/m 2/day [d] + cyclophosphamide 250 mg/m 2/d for 3 d) and followed by a single tisa-cel infusion (0.6-6×10 8 CAR-T cells). Arm B received investigator choice of PCT regimen followed by aHCT in responders or a second PCT in nonresponders. Disease assessments were performed at 6 and 12 weeks (wk), then planned every 3 mo for year (y) 1 and every 6 mo for y 2. The primary endpoint was event-free survival (EFS), defined as time from randomization to stable disease (SD) or progressive disease (PD) at or after wk 12 assessment or death at any time. SD/PD at wk 6 was not considered an event on either Arm. Arm A's wk 6 assessment evaluated disease burden before tisa-cel infusion and after bridging if administered. Arm B's wk 6 assessment determined if response was sufficient for aHCT or if a second PCT regimen was needed prior to aHCT. Results: As of May 6, 2021, 322 pts were randomized: 162 to Arm A and 160 to Arm B. In Arms A and B, 33% and 29% were ≥65 y, and 66% and 67% had primary refractory disease, respectively. Baseline characteristics indicated imbalances with more high-grade B-cell lymphomas (24% vs 17%) and IPI ≥2 (65% vs 58%) in Arm A vs B. In Arm A, 47% received ≥2 cycles of bridging PCT, 36% received 1 cycle, and 17% received 0. In Arm A, 96% received tisa-cel; the median dose was 2.9×10 8 cells. In Arm B, 96% received ≥2 PCT cycles and 54% received ≥2 different PCT regimens; 33% received aHCT, including 10% requiring ≥2 different PCT regimens before aHCT. Median time from randomization to aHCT was 92 d (range, 61-158 d). Median follow-up was 10 mo (range, 2.9-23.2 mo). At wk 6 assessment, 26% had PD in Arm A vs 14% in Arm B. Median EFS in Arms A and B was 3 mo (HR 1.07; 95% CI, 0.82-1.40; P=0.69); Arm A pts with PD at wk 6 had shorter EFS. Overall response rate (ORR) at wk 12 in Arm A was 46% vs 43% in Arm B; complete response rate in both arms was 28%. Some pts responded to tisa-cel after SD/PD at wk 12 without additional tx but were counted as an event in EFS analysis. In Arm B, 81 pts (51%) crossed over to receive tisa-cel, 71 without receiving aHCT. Of 72 crossover pts with response assessment, ORR to tisa-cel was 40%. Overall survival was immature at data cutoff. In Arm A, 84% had a grade ≥3 adverse event (AE; vs 90% in Arm B), including grade ≥3 cytokine release syndrome in 5% (CRS; Lee 2014) and grade ≥3 neurologic events (NE) in 3% (CTCAE v5.0), with no grade 5 CRS/NE. Median times to CRS and NE onset were 4 and 5 d, respectively; median time to resolution was 5 and 9 d. Fifty-two (32%) and 45 (28%) pts in Arms A and B died on study, including 42 (26%) and 32 (20%) deaths due to PD, respectively. Ten pts in Arm A and 13 in Arm B died of AEs. Conclusions: Tisa-cel as 2L tx in R/R aNHL pts did not have a higher EFS vs SOC. Possible contributing factors include study design elements, such as optional PCT bridging tx in Arm A with potential delay of tisa-cel infusion until after wk 6 assessment, allowance of a different PCT regimen to reach aHCT in Arm B after inadequate response to first PCT, and imbalances in relevant pt characteristics. Insights from this randomized Phase III study will inform use of cellular tx in the 2L R/R aNHL setting and the design of future CAR-T trials. Figure 1 Figure 1. Disclosures Bishop: Arcellx, Autolus, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis: Consultancy, Research Funding; Bristol-Myers Squibb and Kite/Gilead: Other: fees for non-CME/CE services . Dickinson: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Amgen: Honoraria. Purtill: Novartis: Honoraria; Gilead: Honoraria; BMS Celgene: Honoraria. Barba: Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Roche, Jazz Phar,aceuticals: Honoraria; Cqrlos III heqlth Institute, aSOCIACION espanola contra el cancer, PERIS: Research Funding. Santoro: Arqule: Consultancy, Speakers Bureau; Sanofi: Consultancy; Takeda: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; AbbVie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eli-Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kato: Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Dainippon-Sumitomo: Honoraria; Eisai: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; MSD: Honoraria; Mundi: Honoraria; Novartis: Consultancy, Research Funding; Ono: Honoraria, Research Funding. Sureda: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy. Greil: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Sandoz: Honoraria, Research Funding. Thieblemont: Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Morschhauser: F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Janssen: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees. Janz: Janssen: Honoraria, Other: Meeting Fees; Novartis: Honoraria; Takeda: Honoraria, Other: Travel Accommodations, Expenses, Meeting fees; Roche: Honoraria; Gilead: Other: Travel Accommodations, Expenses, Meeting fees. Flinn: Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; Seattle Genetics: Research Funding; Sarah Cannon Research Institute: Current Employment; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding. Kwong: Novartis: Consultancy, Honoraria, Research Funding. Kersten: Novartis: Consultancy, Honoraria, Other: Travel support; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Research Funding; Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; BMS/Celgene: Consultancy, Honoraria. Minnema: Janssen: Consultancy, Honoraria; Celgene: Other: Travel expenses; BMS: Consultancy; Kite/Gilead: Consultancy; Alnylam: Consultancy. Holte: Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Nanovector: Membership on an entity's Board of Directors or advisory committees, Other: lectures honorarias; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Nordic: Membership on an entity's Board of Directors or advisory committees. Martinez-Lopez: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees. Maziarz: Novartis: Consultancy, Other: Data and Safety Monitoring board, Research Funding; Incyte Corporation: Consultancy, Honoraria; Bristol-Myers, Squibb/Celgene,, Intellia, Kite: Honoraria; Allovir: Consultancy, Research Funding; Artiva Therapeutics: Consultancy; CRISPR Therapeutics: Consultancy; Intellia: Honoraria; Omeros: Research Funding; Athersys: Other: Data and Safety Monitoring Board, Patents & Royalties; Vor Pharma: Other: Data and Safety Monitoring Board. McGuirk: Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Novartis: Research Funding; Fresenius Biotech: Research Funding; Astelllas Pharma: Research Funding; Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding; Gamida Cell: Research Funding; Pluristem Therapeutics: Research Funding. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Dreyling: Amgen: Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Gilead Kite: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; AbbVie: Research Funding; BeiGene: Consultancy, Speakers Bureau; Genmab: Consultancy; MorphoSys: Consultancy. Harigae: Bristol Myers Squibb: Honoraria; Novartis Pharma: Honoraria, Research Funding; Chugai Pharma: Honoraria; Janssen Pharma: Honoraria; Ono pharma: Honoraria, Other: Subsidies or Donations; Astellas Pharma: Other: Subsidies or Donations; Kyowakirin: Other: Subsidies or Donations. Bond: Kite/Gilead: Honoraria. Andreadis: Merck: Research Funding; BMS: Research Funding; CRISPR Therapeutics: Research Funding; GenMAB: Research Funding; Novartis: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Epizyme: Honoraria; Incyte: Honoraria; TG Therapeutics: Honoraria; Kite: Honoraria; Karyopharm: Honoraria; Atara: Consultancy, Honoraria. McSweeney: Kite-Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gamida: Consultancy, Honoraria; TG Theraputics: Consultancy, Honoraria; Autolous Limited: Research Funding; Novartis: Research Funding; NKARTA: Research Funding; Allovir: Research Funding. Newsome: Novartis: Current Employment. Degtyarev: Novartis: Current Employment, Current equity holder in publicly-traded company. Del Corral: Novartis: Current Employment. Andreola: Novartis: Current Employment, Current holder of stock options in a privately-held company. Masood: Novartis: Current Employment, Current holder of stock options in a privately-held company. Schuster: AbbVie, Acerta, Celgene/Juno, DTRM Bio, Genentech, Incyte, Merck, Novartis, Portola, and TG Therapeutics: Research Funding; Acerta, AlloGene, AstraZeneca, BeiGene, Celgene/Juno, Genentech/Roche, LoxoOncology, Novartis, and Tessa Therapeutics: Consultancy; Acerta, AlloGene, AstraZeneca, BeiGene, Celgene, Genentech/Roche, LoxoOncology, Novartis, Nordic Nanovector, Pfizer, and Tessa Therapeutics;: Honoraria; Novartis: Other: Personal fees, Patents & Royalties; AbbVie, Celgene, Novartis, Juno, Nordic Nanovector, and Pfizer: Other: Steering Committee Participation. Jaeger: BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Norvartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Westin: Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Umoja: Consultancy; Iksuda Therapeutics: Consultancy; Curis: Research Funding; Morphosys: Research Funding; 47 Inc: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 3
    In: Blood, American Society of Hematology, Vol. 140, No. 21 ( 2022-11-24), p. 2193-2227
    Abstract: With the introduction of large-scale molecular profiling methods and high-throughput sequencing technologies, the genomic features of most lymphoid neoplasms have been characterized at an unprecedented scale. Although the principles for the classification and diagnosis of these disorders, founded on a multidimensional definition of disease entities, have been consolidated over the past 25 years, novel genomic data have markedly enhanced our understanding of lymphomagenesis and enriched the description of disease entities at the molecular level. Yet, the current diagnosis of lymphoid tumors is largely based on morphological assessment and immunophenotyping, with only few entities being defined by genomic criteria. This paper, which accompanies the International Consensus Classification of mature lymphoid neoplasms, will address how established assays and newly developed technologies for molecular testing already complement clinical diagnoses and provide a novel lens on disease classification. More specifically, their contributions to diagnosis refinement, risk stratification, and therapy prediction will be considered for the main categories of lymphoid neoplasms. The potential of whole-genome sequencing, circulating tumor DNA analyses, single-cell analyses, and epigenetic profiling will be discussed because these will likely become important future tools for implementing precision medicine approaches in clinical decision making for patients with lymphoid malignancies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 4
    In: Blood, American Society of Hematology, Vol. 139, No. 2 ( 2022-01-13), p. 256-280
    Abstract: ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 5
    In: Blood Advances, American Society of Hematology, Vol. 6, No. 15 ( 2022-08-09), p. 4553-4557
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 6
    In: Blood, American Society of Hematology, Vol. 140, No. 11 ( 2022-09-15), p. 1200-1228
    Abstract: The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CACs) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As a continuation of this CAC-based process, the authors, a group with expertise in the clinical, pathologic, and genetic aspects of these disorders, developed the International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias. Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 7
    In: Blood Advances, American Society of Hematology, Vol. 6, No. 13 ( 2022-07-12), p. 3997-4005
    Abstract: CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 8
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 1022-1024
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 5-6
    Abstract: Introduction: Letermovir is a terminase complex inhibitor that was recently approved for prevention of cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant (HCT). Its favorable side effect profile makes it an attractive alternative to other anti-CMV agents. Nevertheless, its use may present other challenges secondary to enzyme induction, leading to clinically significant drug-drug interactions. Voriconazole is widely used for prophylaxis against invasive fungal infections in the setting of HCT. By virtue of its hepatic metabolism mediated by CYP2C19, the package insert recommends close monitoring of voriconazole trough concentration when given concomitantly with letermovir. The objective of this study was to characterize the extent of interaction between voriconazole and letermovir in allogeneic HCT recipients. The study was approved by the institutional review board. Methods: Patient selection and data collection: An institutional database was queried to identify patients who underwent allogeneic HCT and received antifungal prophylaxis with voriconazole from November 2018 through July 2020. Per the institutional standard operating procedure (SOP), patients initially received intravenous micafungin 50 mg daily which was switched to voriconazole when oral drug administration became feasible. The voriconazole prophylactic dose was guided by CYP2C19 phenotype. Rapid metabolizers (harboring the gain of function variantCYP2C19*17) received 300 mg twice daily whereas others received 200 mg twice daily. Further dose adjustment was warranted if trough concentration, measured at least 5 days after starting voriconazole, did not fall within target range of 1 to 5.5 mg/L. Patients at risk for CMV reactivation who underwent HCT after SOP revision (November 2019) received prophylaxis with letermovir 480 mg daily on day +6 post HCT. After a retrospective review of electronic medical records, HCT recipients were divided into two cohorts;cohort 1included patients who received letermovir prophylaxis whereascohort 2comprised those who did not. Data extracted from medical records included: demographics, hematological disorder, voriconazole dose and trough concentration, and date of letermovir initiation. Statistical analysis: The Student's t-test was used to compare mean voriconazole trough plasma concentration between cohorts 1 and 2. The chi-squared/Fisher's exact test was used to compare rate of subtherapeutic voriconazole trough concentration. Multivariate logistic regression analysis was performed to determine the association between letermovir use and subtherapeutic voriconazole concentration after adjusting for age, gender, race, weight and voriconazole dose. All statistical analyses were performed in SAS (version 9.4) Results: 64 patients were identified (23 in cohort 1 and 41 in cohort 2). Baseline characteristics were comparable except for age (62.0±8.7 years in cohort 1 vs. 58.0±12.2 years, p=0.01); 39% of patients in cohort 1 and 30% in cohort 2 received voriconazole 300 mg twice daily upfront for prophylaxis due to the rapid CYP2C19 metabolizer phenotype whereas the rest received voriconazole 200 mg twice daily (p=0.6). There was no significant difference in mean voriconazole trough plasma concentration (p=0.5) or frequency of subtherapeutic trough (p=0.16) between cohorts 1 and 2 (Figure 1). Multivariate logistic regression analysis indicated that letermovir prophylaxis had no impact on subtherapeutic voriconazole concentration (OR: 0.4, 95% CI: 0.1-1.4, p=0.1). In the subgroup of patients who received voriconazole at 300 mg twice daily, the rate of subtherapeutic concentration did not differ significantly between cohorts 1 and 2 (p=1.0), whereas a non-significant trend in rate of subtherapeutic voriconazole concentration was noted in subgroup of patients who received the 200 mg dose (p=0.1,Figure 2) Conclusions: Our single center experience suggests there may not be a significant interaction between voriconazole and letermovir. Notably, patients receiving the 300 mg dose upfront may not require an additional dose increase to achieve a voriconazole trough within the recommended range despite the concomitant use of letermovir. Our group is collaborating with other centers to corroborate these findings, particularly in patients receiving the standard voriconazole prophylactic dose of 200 mg. Disclosures Grunwald: Forma Therapeutics:Research Funding;Agios:Consultancy;Abbvie:Consultancy;Trovagene:Consultancy;Daiichi Sankyo:Consultancy;Astellas:Consultancy;Daiichi Sankyo:Consultancy;Trovagene:Consultancy;Trovagene:Consultancy;Premier:Consultancy;Astellas:Consultancy;Astellas:Consultancy;Genentech/Roche:Research Funding;Premier:Consultancy;Genentech/Roche:Research Funding;Genentech/Roche:Research Funding;Premier:Consultancy;Janssen:Research Funding;Merck:Consultancy;Forma Therapeutics:Research Funding;Incyte:Consultancy, Research Funding;Celgene:Consultancy;Incyte:Consultancy, Research Funding;Incyte:Consultancy, Research Funding;Pfizer:Consultancy;Celgene:Consultancy;Celgene:Consultancy;Cardinal Health:Consultancy;Merck:Research Funding;Daiichi Sankyo:Consultancy;Agios:Consultancy;Abbvie:Consultancy;Merck:Consultancy;Amgen:Consultancy;Merck:Consultancy;Amgen:Consultancy;Abbvie:Consultancy;Pfizer:Consultancy;Amgen:Consultancy;Pfizer:Consultancy;Agios:Consultancy;Cardinal Health:Consultancy;Forma Therapeutics:Research Funding;Cardinal Health:Consultancy;Janssen:Research Funding.Ai:Incyte:Speakers Bureau;Celgene:Speakers Bureau.Knight:Foundation for Financial Planning:Research Funding.Chojecki:Incyte:Research Funding;Novartis:Other: Investigator Meeting Attendance.Avalos:Juno:Membership on an entity's Board of Directors or advisory committees;Best Practice-Br Med J:Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia.Copelan:Amgen:Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 10
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2635-2635
    Abstract: The use of novel small molecule inhibitors alone or in combination with anti-CD20 monoclonal antibodies for chronic lymphocytic leukemia (CLL) has raised a number of questions on efficacy, tolerability, long-term treatment adherence in patients with heterogeneous clinical features. To fill this gap, we designed a study focusing on treatment sequencing in patients with CLL in order to (i) compare the outcome of patients treated with chemoimmunotherapy (CIT) combinations in first-line versus those receiving Bruton's tyrosine kinase inhibitors (BTKi); (ii) characterize the efficacy and tolerability of venetoclax-based regimens; (ii) understand the impact of treatment sequencing when it comes to chemo-free options including venetoclax after BTKi and vice versa. Data from consecutive sets of patients diagnosed with CLL between 2000-2020 attended at 77 institutions affiliated with ERIC were collected and analyzed. Collected variables included: demographics, clinical stage at diagnosis, IGHV gene somatic hypermutation status; cytogenetic status for chromosomes 11q, 13q 17p and 12 determined by fluorescence in situ hybridization; TP53 gene mutation status; treatment; treatment response; discontinuation; reason for discontinuation; death. We included 9173 patients with a diagnosis of CLL who received at least one line of treatment. The median age at diagnosis was 67 years with a male:female ratio of 1.9. The median follow-up was 78 months (IQR, 48-120 months). Regarding novel targeted agents, 1860/9173 (20.2%) patients had received at least one line of treatment with BTKi (ibrutinib, n=1788; acalabrutinib, n=72) over the disease course; 631/9173 (6.9%) with venetoclax; and, 447/9173 (4.9%) with the PI3K inhibitor idelalisib. Seventy-nine patients were treated with both BTKi and venetoclax (59 BTKi followed by BCL2i, 20 vice versa). At last follow-up, 5870/9173 patients (64.0%) were alive, 3229/9173 (35.2%) died and 74/9173 (0.8%) were lost to follow-up. Patients treated with BTKi in first-line were enriched for TP53 aberrations [del(17p) 27.6%, TP53 mutation 26.3%] and unmutated IGHV genes (69%) and obtained an ORR of 87.7%. Of these, 136 (26.3%) discontinued treatment after a median of 1.2 years (0.07-5.98); main reasons of discontinuation were toxicity (40.5%) and failure (26.2%). Among 631 patients treated with venetoclax at any line, 100 (15.8%) received BCL2 +/- anti-CD20 as first-line; 170 (26.9%) as second line (125 previously treated with CIT, 27 with BTKi); and, 361 as third or subsequent line. ORR ranged between 71.5% (≥3 lines) with 30.5% CR/CRi to 90.3% (first-line) with 68.1% CR/CRi. Treatment discontinuation was due to toxicity in 28.6% of patients treated in the first-line, and 17.6% and 21.8% of patients treated in second and third-or-higher-line, respectively. Disease progression led to treatment discontinuation in 14.3%, 20.6% and 33.6% in first, second and third-or-higher line, respectively. CIT was used as front-line treatment in 5465 patients (59.6%). Of these, 2070 (37.9%) and 1018 (18.6%) patients received a second and third line of treatment, respectively. The great majority (865/1086 cases, 79.7%) of patients who received a second line before 2014 were retreated with CIT, most commonly Bendamustine-Rituximab (284/1086, 26.1%) and Fludarabine-Cyclophosphamide-Rituximab (252/1086, 23.2%); alemtuzumab monotherapy was used in 55/1086 (5%) of patients. After 2014, 415/984 patients (42.1%) were retreated with BTKi; 93 (9.5%) with venetoclax; 70 (7.2%) with idelalisib; 50 (5%) with Alemtuzumab monotherapy, and 315 (32%) with CIT. Similarly, in the third-or-higher line of treatment, most patients (86.3%) were retreated with CIT before 2014, while BTKi, BCL2i, and PI3Ki were mainly used after 2014 (in 43.1%, 15.7% and 14.7% of cases, respectively). Finally, our cohort included 1075 patients with TP53 aberrations. The ORR of patients receiving BTKis (n=171) as first-line of treatment was 86.5% (22.2 CR+64.3 PR), while the ORR with venetoclax +/- anti-CD20 (n=15) was 91% (45.5% CR+45.5 PR). Patients treated with CIT (n=694) had an ORR of 68.7% (28.3% CR+40.4% PR). In conclusion, in a large international study we provide real world data regarding the selection and sequencing of treatment in CLL, charting a major shift in treatment patterns before and after the introduction of novel trargeted agents and confirming their efficacy even in high-risk CLL. Disclosures Scarfo: Janssen: Honoraria, Other: Travel grants; Astra Zeneca: Honoraria; Abbvie: Honoraria. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Collado: Abbvie,: Other: pharmaceutical Company, Research Funding; Janssen: Other: Pharmaceutical Company, Research Funding. Galimberti: AbbVie, Janssen: Honoraria, Other: Travel grants; Incyte: Speakers Bureau. García-Serra: AbbVie: Other: Educational grands; Janssen: Other: Educational grants; Novartis: Other: Educational grants. Gozzetti: Janssen: Honoraria; AbbVie: Honoraria. Hatzimichael: Amgen, Roche, Genesis, Novartis, Bristol Mayer Squibb, Celgene, Pfizer: Consultancy; Abbvie, Amgen, Bristol Mayer Squibb, MSD, Gilead, Janssen Cilag, Genesis Pharma, Roche, Takeda: Honoraria. Herishanu: AbbVie: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Medison: Honoraria. Jaksic: Roche, Oktal-Pharma/Celtrion, Sandoz: Consultancy, Honoraria. Kater: Janssen, AstraZeneca: Other: Ad Board, steering committee, Research Funding; Abbvie: Honoraria, Other: Ad Board, Research Funding; BMS, Roche/Genentech: Other: Ad Board, , Research Funding; Genmab, LAVA: Other: Ad Board, Steering Committee. Kotsianidis: Astellas: Other: NONE, Research Funding, Speakers Bureau; Genesis: Consultancy, Other: NONE; Janssen Hellas: Consultancy, Other: NONE, Speakers Bureau; Bristol Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Novartis Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Abbvie: Consultancy, Other: NONE, Research Funding, Speakers Bureau. Kreitman: NIH: Patents & Royalties: Moxetumomab Pasudotox; Genentech: Research Funding; Teva: Research Funding; AstraZeneca/MedImmune: Research Funding; Innate: Research Funding; GSK/Novartis: Research Funding; Array BioPharma/Pfizer: Research Funding. Laribi: BeiGene: Other: Personal Fees; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; Takeda: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees. Lopez-Garcia: Roche: Other: Speaker Honoraria, Travel and accommodation grants; Novonordisk: Other: Speaker Honoraria; Fresenius: Other: Speaker Honoraria; Celgene: Other: Speaker Honoraria; Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants; Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding. Milosevic: Roche: Honoraria; Abbvie,: Honoraria; Janssen: Honoraria; Sandoz: Honoraria. Reda: Beigene: Consultancy; Astra Zeneca: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Šimkovič: Janssen, Gilead, Roche, AstraZeneca, and AbbVie: Other: consultancy fees, advisory board participation fees, travel grants, and honoraria; University Hospital Hradec Kralove: Current Employment; AbbVie: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Merck: Current equity holder in publicly-traded company; Eli Lilly: Current equity holder in publicly-traded company; J & J: Current equity holder in publicly-traded company; Gilead: Other: Travel, Accommodations, Expenses. Špaček: AbbVie, AstraZeneca, Gilead, Janssen, and Roche: Honoraria. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Visentin: Italfarmaco and Gilead: Speakers Bureau. Vassilakopoulos: AstraZeneca: Honoraria; Amgen: Honoraria, Research Funding; Pfizer: Research Funding; Dr. Reddy's: Research Funding; Novartis: Consultancy, Honoraria; GlaxoSmithKline: Honoraria, Other: Travel; Merck: Honoraria, Research Funding; Integris: Honoraria; Roche: Consultancy, Honoraria, Other: Travel; Genesis Pharma: Consultancy, Honoraria, Other: Travel; Takeda: Consultancy, Honoraria, Other: Travel, Research Funding; AbbVie: Consultancy, Honoraria; Karyopharm: Research Funding. Vitale: Janssen: Honoraria. Yáñez: Gilead-Kite, Janssen, AbbVie, AstraZeneca, Beigene, Roche, Pfizer, Jazz, BMS, and Merck: Other: Advisory board participation fees ; Janssen, AbbVie, AstraZeneca, Gilead-Kite, Roche, Pfizer, and Merck: Speakers Bureau. Antic: AbbVie, Janssen, and Roche: Honoraria. Coscia: Janssen: Honoraria, Other, Research Funding; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria, Other. Cuneo: AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Gaidano: Beigene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Guièze: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Laurenti: AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Tam: Beigene: Research Funding; Janssen: Research Funding; Abbvie: Research Funding; Loxo: Honoraria; Beigene: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Trněný: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Celgene: Consultancy; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Bosch Albareda: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Abbvie: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Kite: Honoraria; Sanofi: Honoraria; Lilly: Honoraria. Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Chatzidimitriou: Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Ghia: AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sunesis: Research Funding. Stamatopoulos: AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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