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  • 1
    In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 94, No. 7 ( 2015-7), p. 1241-1243
    Type of Medium: Online Resource
    ISSN: 0939-5555 , 1432-0584
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
    detail.hit.zdb_id: 1458429-3
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  • 2
    In: European Journal of Cancer, Elsevier BV, Vol. 150 ( 2021-06), p. 143-154
    Type of Medium: Online Resource
    ISSN: 0959-8049
    RVK:
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 3
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 3, No. 5 ( 2015-05-01), p. 547-556
    Abstract: The antibody-based delivery of IL2 to extracellular targets expressed in the easily accessible tumor-associated vasculature has shown potent antileukemic activity in xenograft and immunocompetent murine models of acute myelogenous leukemia (AML), especially in combination with cytarabine. Here, we report our experience with 4 patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, in combination with low-dose cytarabine. One patient with disseminated extramedullary AML lesions achieved a complete metabolic response identified by PET/CT, which lasted 3 months. Two of 3 patients with bone marrow relapse achieved a blast reduction with transient molecular negativity. One of the 2 patients enjoyed a short complete remission before AML relapse occurred 2 months after the first infusion of F16-IL2. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells in the bone marrow. Grade 2 fevers were the only nonhematologic side effects in 2 patients. Grade 3 cytokine-release syndrome developed in the other 2 patients but was manageable in both cases with glucocorticoids. The concept of specifically targeting IL2 to the leukemia-associated stroma deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT. Cancer Immunol Res; 3(5); 547–56. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 4
    In: Cancers, MDPI AG, Vol. 14, No. 3 ( 2022-01-23), p. 565-
    Abstract: Prognosis of elderly ALL patients remains dismal. Here, we retrospectively analyzed the course of 93 patients 〉 55 years with B-precursor (n = 88) or T-ALL (n = 5), who received age-adapted, pediatric-inspired chemotherapy regimens at our center between May 2003 and October 2020. The median age at diagnosis was 65.7 years, and surviving patients had a median follow-up of 3.7 years. CR after induction therapy was documented in 76.5%, while the rate of treatment-related death within 100 days was 6.4%. The OS of the entire cohort at 1 and 3 year(s) was 75.2% (95% CI: 66.4–84.0%) and 47.3% (95% CI: 36.8–57.7%), respectively, while the EFS at 1 and 3 years(s) was 59.0% (95% CI: 48.9–69.0%) and 32.9% (95% CI: 23.0–42.8%), respectively. At 3 years, the cumulative incidence (CI) of relapse was 48.3% (95% CI: 38.9–59.9%), and the CI rate of death in CR was 17.3% (95% CI: 10.9–27.5%). Older age and an ECOG 〉 2 represented risk factors for inferior OS, while BCR::ABL1 status, immunophenotype, and intensity of chemotherapy did not significantly affect OS. We conclude that intensive treatment is feasible in selected elderly ALL patients, but high rates of relapse and death in CR underline the need for novel therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 5
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3365-3365
    Abstract: Introduction: Prognosis of elderly ALL patients is generally considered to be poor. Nonetheless, data on disease characteristics, treatment and outcome of this group of patients is scarce. Methods: Between May 2003 and October 2020, 96 patients (pts) aged & gt; 55 years with B-precursor ALL (91 pts) or T-ALL (5 pts), received first-line induction chemotherapy (84 pts) or were admitted for salvage treatment (8 pts) or allogeneic stem cell transplantation (alloSCT, 4 pts) at the University Hospital Muenster, Germany. 78 patients were diagnosed with a common-ALL (27 pts were BCR/ABL positive) and 13 patients with a pro-B-ALL. Age adapted BFM (Berlin-Frankfurt-Muenster)-like treatment regimens, according to the recommendations of the GMALL (German multicenter ALL study group) for younger (18-55 years, 25 pts) or elderly patients ( & gt; 55 years, 68 pts) were used. In general, these protocols consisted of two cycles of induction therapy followed by consolidation, reinduction and consolidation therapy blocks in the 1 st year as well as a consecutive maintenance therapy in the 2 nd year. 3 patients (3%) received no intensive treatment due to poor performance status and comorbidities. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank-test and Cox proportional hazards model for RFS and OS, respectively. Results: Median patient age at diagnosis was 66 years (range 55-89 years). 94% of all patients had an ECOG (Eastern Cooperative Oncology Group) status of 0-2 and 92% had a Charlson comorbidity index of 0-2. The median follow-up of all patients was 2.0 years (range 20 days - 16.9 years) and of surviving patients 3.7 years (range 8.8 months - 16.9 years). A complete remission (CR) after induction therapy was documented in 62 of 81 (77%) patients receiving their initial induction therapy at our center. Minimal residual disease (MRD) status was analyzed by quantitative real time PCR in 44 of these patients and 19 patients had an MRD negative CR (43%) after induction therapy. The rate of early death after intensive therapy (death within 100 days after start of treatment) was 6%. The 3 patients not treated with intensive chemotherapy died within 3 months. 27 of 93 patients finished the first year of treatment. Subsequent maintenance therapy was administered to 12 patients. The reasons for discontinuation of conventional treatment in the first and second year were relapsed disease (31 pts), alloSCT in 1 st CR (23 pts), toxicity/patients' preference (17 pts) and death in CR under conventional therapy (7 pts). 3 patients have not completed their therapy yet. OS and RFS of the entire cohort at 1 year were 73% (95% CI: 64-82%) and 57% (95% CI: 47-67%) and at 3 years 46% (95% CI: 36-56%) and 32% (95% CI: 22-42%), respectively. The cumulative incidence of relapse at 1 and 3 years was 29% (95% CI: 20-41%) and 56% (95% CI: 45-69%), respectively. OS of those patients receiving an alloSCT (23 pts in 1 st CR, 7 pts in 2 nd CR, 3 pts with active disease, median age at alloSCT 62 years) at 1 and 3 years was 82% (95% CI: 68-95%) and 49% (95% CI: 32-67%), respectively. The cumulative incidence of relapse after alloSCT at 1 and 3 years was 16% (95% CI: 7-35%) and 32% (95% CI: 18-56%), respectively. Regarding the entire patient cohort, older age ( & gt; 75 years, 15 pts) was significantly associated with an inferior OS (p & lt; .001). BCR/ABL status, ALL phenotype (T- or B-ALL) or intensity of conventional treatment applied (protocol originally intended for patients ≤ 55 years vs & gt; 55 years) had no significant impact on OS. In multivariate analysis, ECOG status & gt;2 and persisting disease after 1 st consolidation therapy were risk factor associated with inferior OS (p & lt; .05). Conclusion: Intensive treatment is feasible in selected elderly ALL patients ( & gt; 55 years). High relapse rates and impaired survival rates underline the need for novel therapeutic strategies. Disclosures Khandanpour: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; BMS/Celgene: Honoraria. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Brüggemann: Incyte: Other: Advisory Board; Amgen: Other: Advisory Board, Travel support, Research Funding, Speakers Bureau; Janssen: Speakers Bureau. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Stelljes: Celgene/BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 980-980
    Abstract: The tumor-directed delivery of therapeutics using monoclonal antibodies specific to a tumor-associated antigen promises to accumulate large doses of the delivered payload at the tumor site while sparing healthy organs. The antibody-based delivery of interleukin-2 (IL-2) to extracellular targets expressed in the easily accessible tumor vasculature has shown promising results in animal models of solid tumors and hematological malignancies. In xenograft and immunocompetent murine models of acute myeloid leukemia (AML), IL-2-based vascular targeting antibody fusions have recently demonstrated potent anti-leukemic activity, especially when used in combination with cytarabine. Here, we report our experiences in four patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, consisting of a human monoclonal antibody specific to spliced large isoforms of tenascin-C fused to human IL-2, in combination with very low dose cytarabine (5 mg subcutaneously twice daily for 10 days). Clinical evidence of anti-leukemia efficacy was shown in all patients. One patient with rapidly progressing disseminated extramedullary AML lesions achieved a complete metabolic response in PET/CT, which lasted three months. Two out of three patients with bone marrow relapse achieved a blast reduction with transient molecular negativity (NPM1). One of the two enjoyed a short complete remission before AML relapse occurred two months after the first infusion of F16-IL2. The other patient did not regenerate neutrophil and thrombocyte counts and showed progressive disease after completion of the first cycle. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells (natural killer cells, CD8+ T cells, γδ T cells) in the bone marrow. Grade 2 fevers were the only non-hematological side effects in two patients. Grade 3 cytokine-release syndrome developed in the other two patients, required hospitalization, but was manageable in both cases with systemic glucocorticoids. No non-hematological grade 4 toxicities were observed. The concept of specifically targeting IL-2 to the leukemia-associated stroma using armed antibodies deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT. Disclosures Off Label Use: In this report, the antibody-cytokine fusion protein F16-IL2 has been used in a compassionate use setting in individual patients presenting with AML relapse after allogeneic stem cell transplantation. F16-IL2 is currently being evaluated in phase I/II studies in patients with solid cancer.. Neri:Philogen SpA: Employment, Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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    detail.hit.zdb_id: 80069-7
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