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  • 1
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2012-12)
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
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  • 2
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5467-5467
    Abstract: BCD-020 (Acellbia, rituximab biosimilar candidate) was shown to be highly similar to innovator rituximab (MabThera®/Rituxan®) in terms of its quality characteristics, in vitro biological activity, as well as toxicology and PK/PD characteristics in non-human primates. International multicenter comparative randomized open-label clinical study was carried out in a period from 2011 to 2013 and involved over 30 centers in Russia, Ukraine and India. Its methodology and design complies with current EMA guidelines on similar biological products containing monoclonal antibodies (EMA/CHMP/BMWP/403543/2010). 92 patients with follicular non-Hodgkin’s lymphoma, stage I-IV by Ann Arbor, or marginal zone lymphoma, stage I-IV by Ann Arbor, ECOG 0-2, who had at least 1 measurable lesion were enrolled. According to study protocol patients with secondary transformed B-cell lymphomas or with highly aggressive types of tumor, bulky disease, severe concomitant somatic disorders and some other conditions were excluded. If a patient had previous story of chemotherapy or radiation he could be included after at least 3 weeks post-treatment. Participation of patients who were previously treated with any kind of monoclonal antibodies was prohibited. After signing standard informed consent form and completion of 28-days screening period eligible patients underwent stratification in accordance to their prognostic risk (FLIPI or IPI) and previous treatment (naïve or pretreated). Subsequently patients were randomized (1:1) into 2 groups: 46 patients were included in the main group where Acellbia (rituximab biosimilar) was administered at a dose of 375 mg/m2 as a slow IV infusion on day 1, 8, 15 and 22; 46 patients were included in the reference group where MabThera was used at the same regimen. Use of any other medicines for the treatment of lymphoma was strictly prohibited. Efficacy was assessed on the basis of computed tomography and bone marrow evaluation which were performed 1 month after the completion of treatment. Median age of patients in each group was 57.5 years (main group [50.0-64.0], reference group [47.0-65.0] ). Manageable comorbidities were reported in 50% of patients in the main group and 34.78% of patients in the reference group, p=0.2053. Comparative analysis of the prognostic risk factors confirmed the equivalence of study groups. The number of pretreated patients in both groups was equal – 8 individuals per group. Statistical analysis didn’t find any difference in overall response rate in general population of patients (39.52% patients in the main group vs. 36.57% patients in the reference group, p=0.8250), as well as in population of pretreated patients (28.6% vs 37.5% respectively, p=1.00) and in population of naïve patients (42.8% vs 39.4% respectively, p=1.00). The lower limit of the two-tailed 95% CI for difference in proportions of ORR was equal to -0.17 and exceeded the predefined non-inferiority margin -0.2, which confirmed non-inferiority of Acellbia to MabThera in terms of efficacy. Treatment-associated AE of any grade were reported in 21.74% patients in both arms, in the absence of statistically or clinically significant difference (p = 0.8005). There were 2 cases of CTCAE 4.03 grade 3-4 AEs in each group. PK and PD parameters were shown to be equivalent in both study groups. Thus, study results suggest that Acellbia has same efficacy and safety in patients with B-cell non-Hodgkin’s lymphoma. Disclosures Chernyaeva: JCS BIOCAD: Employment. Ivanov:JCS BIOCAD: Employment. Isaev:JCS BIOCAD: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5072-5072
    Abstract: Introduction. MRD-tailored therapy based on pediatric-inspired intensification is a back-bone of the majority of the European study groups in adult ALL. Taking in consideration the major pitfalls of the first Russian acute lymphoblastic leukemia study group trial RALL-2009 (NCT01193933) - high CR death rate, early CNS relapses in T-ALL, selection bias in auto-HSCT vs chemotherapy comparison, absence of MRD monitoring - a new RALL-2016 protocol (NCT03462095) was introduced based on the same principles as the first one - non-intensive but non-interruptive approach with low numbers of allo-HSCT, but with further deintensification of consolidation phase, centralized MRD-monitoring and randomization for autologous HSCT with non-myeloablative conditioning (CEAM). AIM. To analyze the 2,5 years efficacy and to determine significance of MRD status after induction in the new Russian ongoing prospective multicenter study RALL-2016. Materials and patients. RALL-2016 was based on the previous RALL-2009 protocol , but one day high-dose MTX and high-dose ARA-C blocks were eliminated and substituted by 2 months of non-interruptive therapy, L-asparaginase was scheduled for 1 year of treatment instead of 2,5 y, 15 intrathecal injections were increased up to 21 mostly while consolidation phase, CR T-ALL patients were brought to randomization after the informed consent: auto-HSCT vs no auto-HSCT, - with the similar further maintenance. All primary bone samples are collected and tested for cytogenetics and molecular markers, all included patients are monitored by flow cytometry by aberrant immunophenotype in a centralized lab. Results and discussion. From Dec 2016 till Jul 2019 148 Ph-negative ALL pts from 10 centers were included: median age 33 y (18-54) (BCP-ALL-80 (54%) pts, T-ALL- 64 (44%), biphenotypic- 4 (2%)). CR was achieved in 84% pts. The induction death before CR was 8% (n=12), refractory ALL was registered in 12 pts (8%). Death in CR occurred in 4%. After CR achievement 52 T-ALL patients were randomized either to chemotherapy (n=25) or to autoHSCT(n= 27). 15 of 27 T-ALL pts were transplanted at a median time of 6 months from CR (1 of 27 received alloHSCT - Neimegen Syndrom, 2 of 27 died in CR before HSCT, one pt refused the autotransplant ). OS and DFS at 2-years constituted 70,7% and 80%. 2-y OS was 65,8% for BCP-ALL, 80% for T-ALL and 66,7% for MPAL (p=0,5). 2-y DFS was 78,7% for BCP-ALL, 83,4% for T-ALL and 100% for MPAL (p=0,88). AlloHSCT in 1st CR have received only 3 (2%) pts. We have registered the differences in OS in pts who were treated in Federal Center (51 pts) or in Regional centers (97pts): 82% vs 64,6%, respectively (p=0,02). But there were no differences in DFS: 87,7% vs 77,3%, respectively (p=0,66) (Pic1). We have detected very high death rate in induction and in CR in the regional Centers despite the fact that the main pts characteristics were similar (median age, hyperleukocytosis, high risk group). MRD persistence after induction (70th day of protocol) became a significant factor of poor prognosis: 2-yeasr OS and DFS in MRD-negative (59 pts) and MRD-positive (33pts) were 91,8% vs 56,4% (p=0,017) and 88,7% vs 64,3% (p=0,16), respectively (Pic 2). Median of relapse was 7 month. Conclusion. The new RALL-2016 study pitifully continues to demonstrate high induction and CR death rate in regional centers despite of de-intensification of chemotherapy. We've observed significant differences in OS in Federal Center vs Regionals Centers, but not in DFS. MRD monitoring by FCM in ALL patients revealed that the persistence of MRD after induction (day+70) was an independent factor of poor prognosis and high relapse rate suggesting the introduction of new treatment approaches within a very short time after induction (maximum 3 months) in MRD positive patients. Figure Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 4
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2497-2497
    Abstract: Introduction It is postulated that the improvement in the overall treatment outcome in adult Ph-negative ALL came from the implementation of more aggressive pediatric-like protocols and higher portion of allogeneic HSCT. Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the opposite approaches: less intensive but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Patients and Methods The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are 〉 25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks prd/dexa with 3 instead of 4 dauno/vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks-continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications- with 1 day HD MTX and with 1 d HD ARA-C, both with L-asp and 3 ds dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11),L 〉 100). No central MRD monitoring was performed. Since Apr 2009 till June 2015 20 centers had recruited 168 BCP-Ph-negative ALL pts with a median age 28 years (15-54), 84f/84 m. Full cytogenetics was available in 67,3% (n=113), 43,4% of them (n=49) had normal karyotype (NK), 10% (n=9%) had no mitosis, 47,6% (n=54) - different abnormalities (hypoploid-1, hyperploid-12, t(11q23)/MLL-8, del11q23-2, t(1;19)-2, t(12;21)-1;others-28). 26,7% of pts (n=45) were in the standard risk (SR) group (WBC 〈 30, EGIL BII-III, LDH 〈 2N; no late CR; t(4;11)-negative), 56,5% (n=95) - in the high risk (HR) group (WBC 〉 30; EGIL BI, LDH 〉 2N; late CR; t(4;11)-positive), 28 patients (n=16,8%) were not qualified by the risk. The analysis was performed in June 2015. 158 pts were available for analysis. Results CR rate in 158 available for analysis pts was 87,7% (n=139), induction death occurred in 9,1% (n=14), resistance was registered in 3,2% (n=5). The majority of CR pts (87,8%) achieved it after prephase (12,2%, n=17) and the 1st phase of induction (75,6%, n=105). Late responders constituted 12,2% (n=17). Allogeneic BMT was performed only in 9 of 144 patients who survived induction (6,2%). Totally 31 pts (22,3%) had relapsed. At 60 mo OS for the whole group constituted - 50%, DFS - 51.3%. In a univariate analysis among various risk factors (age 〈 〉 30y, initial risk group, WBC, LDH, immunophenotype, late response 〉 35d, PRD resistance) age ( 〉 30 y) became statistically significant for OS, DFS and relapse probability (RP) (pic.1), abnormal karyotype - for DFS (30% vs 68%, p=0,04) and RP (42% vs 19%, p= 0,04). In a multivariate analysis no common risk factors were significant. Conclusions Our data demonstrate that the proposed treatment approach is rather effective. We believe that constant non-interruptive treatment without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that it should be very strict compliance of the pts to the protocol. All pts, mostly from the region hospitals who refused prolonged and constant treatment (~5%), relapsed. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 5
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 23, No. 8 ( 2023-08), p. 589-598
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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    detail.hit.zdb_id: 2193618-3
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  • 6
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 22 ( 2022-10), p. S166-
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 7
    In: The Lancet Oncology, Elsevier BV, Vol. 17, No. 3 ( 2016-03), p. 319-331
    Type of Medium: Online Resource
    ISSN: 1470-2045
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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  • 8
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4994-4994
    Abstract: Background: Research on the impact of COVID-19 on different patient populations has been of great value for the optimization of patient care since the start of the SARS-CoV-2 pandemic. Earlier, we reported the interim analysis of the immediate outcomes in patients (pts) with hematologic (hem) disease and COVID-19. Long-term results of the CHRONOS19 registry are now available. Methods: CHRONOS19 is an observational prospective cohort study among adult pts ((≥18 years) with hem diseases (malignant or non-malignant) and laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 in Russia. Data from 15 centers all over the country were collected on a web-based platform in a de-identified manner at 30, 90, and 180 days after COVID-19 was diagnosed. The primary endpoint was 30-day all-cause mortality. Secondary outcomes included COVID-19 complications, rate of ICU admission and mechanical ventilation, outcomes of hem disease in SARS-CoV-2 infected pts, overall survival, and risk factors for disease severity and mortality. Results: As of July 30, 2021, 666 pts were enrolled (females / males [n (%)]: 317 (48%) / 349 (52%); median [range] age: 56 [18-90] years. Disease types (malignant/non-malignant [n (%)] ): 618 (93%) / 48 (7%), including AML 115 (17%), MM 113 (17%), NHL 106 (16%), CML / CMPD 92 (14%), ALL 52 (8%), CLL 50 (8%), MDS 25 (4%), HCL 23 (3%), HL 21 (3%), AA 16 (2%), APL 11 (2%), others 42 (6%); among them induction phase / remission / relapse or refractory / NA in 237 (35%) / 231 (35%) / 152 (23%) / 46 (7%) pts. Concomitant conditions were reported in 385 (58%) pts: cardiovascular 254 (66%), diabetes 76 (20%), obesity 57 (15%), pulmonary 41 (11%), chronic renal 44 (11%) or hepatic 33 (9%) disease, other 90 (23%). At a median follow-up of 7,5(1-19) months, 618 pts were evaluable for the primary outcome. Thirty-day all-cause mortality was 16% (100 pts died). Death due to COVID-19 complications occurred in 82 pts, 14 pts died due to progression of hem disease. Overall, 217 (33%) pts had severe disease, COVID-19 complications were detected in 458 (70%) pts, the most common were pneumonia in 425 (93%) pts, respiratory failure in 252 (55%) pts, multiple organ failure in 56 (12%) pts, cytokine storm in 52 (11%) pts, ARDS in 47 (10%) pts, and sepsis in 44 (10%) pts. The rate of ICU admission was 23% (145 pts) with high mortality in this group of pts (77%), 111 (17%) pts required mechanical ventilation, among them only 5 (4.5%) pts survived. Treatment of hem disease was changed, interrupted, or discontinued in 395 (60%) pts with a median delay of 4 weeks. At 30 days, the rate of relapse / progression of hem disease was 5% / 8% (24 / 40 of 517 evaluable pts). At the longer follow-up (90 and 180 days), relapse / progression occurred in another 9 / 23 pts. At the data cutoff, the median overall survival was not reached. Antibody detection was performed in 253 pts: 211 (84%) pts had IgG to SARS-CoV-2. In a univariate analysis, older age ( & gt; 60 years), myelotoxic agranulocytosis, transfusion dependence, diabetes among comorbidities, ARDS and other complications, except CRS, ICU and mechanical ventilation (Fig. 1) were associated with higher risks of mortality (p & lt;0.05). The final results of the CHRONOS19 study will be presented. Conclusions: Patients with hem disease and COVID-19 have higher mortality than a general population with SARS-CoV-2 infection, predominantly due to COVID-19 complications. The longer-term follow-up did not reveal any concerns in terms of hem disease outcomes. Figure 1 Figure 1. Disclosures Vorobyev: Janssen, Roche, Sanofi, Takeda, Biocad, Abbvie: Other: Advisory Boards, Speakers Bureau; Astellas, Novartis, AstraZeneca: Speakers Bureau. Chelysheva: Pharmstandart: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Novartis Pharma: Speakers Bureau.
    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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  • 9
    In: Cellular Therapy and Transplantation, Foundation for the Development of Bone Marrow Transplantation, Vol. 5, No. 3 ( 2016-09-30), p. 67-70
    Type of Medium: Online Resource
    ISSN: 1866-8836
    Uniform Title: Эпидемиология и результаты лечения ВИЧ-ассоциированных лимфом: многоцентровое ретроспективное исследование
    URL: Issue
    Language: Unknown
    Publisher: Foundation for the Development of Bone Marrow Transplantation
    Publication Date: 2016
    detail.hit.zdb_id: 2442744-5
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  • 10
    In: Voprosy Onkologii, Autonomous non-profit scientific and medical organization - Questions of Oncology, Vol. 68, No. 6 ( 2022-12-27), p. 786-796
    Abstract: Введение. Лимфома Беркитта (ЛБ) ― высокоагрессивная В-клеточная неходжкинская лимфома, составляет до 40% лимфом у пациентов с ВИЧ-инфекцией. Широкое применение антиретровирусной терапии (АРВТ) способствовало улучшению результатов противоопухолевой химиотерапии (ПХТ) лимфом на фоне ВИЧ-инфекции, в том числе ЛБ. Терапии ЛБ в РФ посвящено только несколько работ, а публикаций о ЛБ у пациентов с ВИЧ-инфекцией нет. Цель работы: изучить клинико-эпидемиологические характеристики и оценить результаты терапии ЛБ у пациентов с ВИЧ-инфекцией в РФ. Материалы и методы. В исследование было включено 37 пациентов с ЛБ на фоне ВИЧ-инфекции, проходивших лечение в 10 центрах РФ в период с 2010 по 2021 гг. Результаты. ЛБ у пациентов с ВИЧ-инфекцией диагностируется в молодом возрасте, с медианой 37 лет (21–58 лет), чаще у мужчин (75,7%), в распространенной стадии (IV стадия Ann Arbor ― 64,7%) и с экстралимфатическими проявлениями (73,5%), включая поражение центральной нервной системы (ЦНС) (16,1%). Основная терапия: EPOCH-подобные курсы (54,1%), блоковые схемы (32,4%). У 76% пациентов противоопухолевая ХТ включала ритуксимаб, у 91,4% ― одновременно с АРВТ. Медиана количества курсов терапии составила 4 (1–8). Общая выживаемость (ОВ) в течение 1 года составила 64% (95% ДИ 38–82%), выживаемость без прогрессирования (ВБП) ― 59% (95% ДИ 34–77%). Поражение ЦНС (p=0.0064), и проведение ПХТ без АРВТ ухудшает ОВ (p=0,00016) и ВБП (p=0,00012). Заключение. Для улучшения результатов терапии и прогноза необходимы проспективные м Введение. Лимфома Беркитта (ЛБ) ― высокоагрессивная В-клеточная неходжкинская лимфома, составляет до 40% лимфом у пациентов с ВИЧ-инфекцией. Широкое применение антиретровирусной терапии (АРВТ) способствовало улучшению результатов противоопухолевой химиотерапии (ПХТ) лимфом на фоне ВИЧ-инфекции, в том числе ЛБ. Терапии ЛБ в РФ посвящено только несколько работ, а публикаций о ЛБ у пациентов с ВИЧ-инфекцией нет. Цель работы: изучить клинико-эпидемиологические характеристики и оценить результаты терапии ЛБ у пациентов с ВИЧ-инфекцией в РФ. Материалы и методы. В исследование было включено 37 пациентов с ЛБ на фоне ВИЧ-инфекции, проходивших лечение в 10 центрах РФ в период с 2010 по 2021 гг. Результаты. ЛБ у пациентов с ВИЧ-инфекцией диагностируется в молодом возрасте, с медианой 37 лет (21–58 лет), чаще у мужчин (75,7%), в распространенной стадии (IV стадия Ann Arbor ― 64,7%) и с экстралимфатическими проявлениями (73,5%), включая поражение центральной нервной системы (ЦНС) (16,1%). Основная терапия: EPOCH-подобные курсы (54,1%), блоковые схемы (32,4%). У 76% пациентов противоопухолевая ХТ включала ритуксимаб, у 91,4% ― одновременно с АРВТ. Медиана количества курсов терапии составила 4 (1–8). Общая выживаемость (ОВ) в течение 1 года составила 64% (95% ДИ 38–82%), выживаемость без прогрессирования (ВБП) ― 59% (95% ДИ 34–77%). Поражение ЦНС (p=0.0064), и проведение ПХТ без АРВТ ухудшает ОВ (p=0,00016) и ВБП (p=0,00012). Заключение. Для улучшения результатов терапии и прогноза необходимы проспективные многоцентровые исследования по лечению ЛБ у пациентов с ВИЧ. ногоцентровые исследования по лечению ЛБ у пациентов с ВИЧ.
    Type of Medium: Online Resource
    ISSN: 0507-3758
    URL: Issue
    Language: Unknown
    Publisher: Autonomous non-profit scientific and medical organization - Questions of Oncology
    Publication Date: 2022
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