RESUMO
Background: The introduction of venetoclax into clinical practice has improved the outcome of patients with relapsed/refractory chronic lymphocytic leukemia (RR-CLL). The results of the MURANO trial published in March 2018 showed significantly longer progression-free survival (PFS) and overall survival (OS) in RR-CLL patients treated with venetoclax and rituximab (VEN-R) comparing to bendamustine and rituximab (BR) and resulted in the approval of VEN-R in the therapy of RR-CLL in the European Union and the United States. It should be noted that the results of registration studies often do not correspond with the data from real-life observations. Aims: To study the clinical efficacy and safety profile of VEN-R treatment in RR-CLL patients outside clinical trials. Methods: We performed retrospective analysis of RR-CLL patients treated with VEN-R in hematology centers of the Polish Adult Leukemia Study Group (PALG) from 2019 to 2021. Results: Clinical data of 117 RR-CLL patients treated with VEN-R were collected. Median patient age upon initiation of VEN-R therapy was 67 years (range 33 - 84 years). Seventy-two patients (61.5%) were men. Median Cumulative Illness Rating Scale (CIRS) was 6 (range 2 -16). Patients were treated with a median of 2 (range 1-9) previous lines of therapy, whereas 32 patients (27.4%) had relapsed following the first line of treatment. Overall, 25 patients (21.4%) had 17p deletion, whereas TP53 mutation was identified in 13 patients (11.1%). The median follow-up was 9.96 months (range 0.27 -29.13). The overall response rate (ORR) was 95.2%. Seventeen patients (14.5%) achieved complete remission (CR), 83 (70.9%) partial remission (PR), while in 5 patients (4.3%) disease progression was noted. In the patients with 17p deletion (n=22) or TP53 mutation (n=11), CR and PR were observed in 4 (12.1%) and 29 (87.9%) patients, respectively. The median PFS in the whole cohort was 20.8 (95% CI 18.43 -not reached) months and the median OS was not reached. In our study none of the analyzed clinico-pathological factors had significant impact on ORR, PFS and OS. During the follow-up time four (3.4%) cases of Richter transformation were diagnosed. There were 18 deaths recorded during the course of observation;3 (16.7%) due to disease progression and 7 (38.9%) due to COVID-19 infection. The others were due to infections other than SARS-CoV-2 (n=3, 16.7%) and the cause of death could not be specified in five cases (27.8%). Eighty-three patients (70.9%) remain on treatment, while treatment was discontinued in thirty-four cases (29.1%). Reasons for therapy discontinuation included patient's death (52.9%), treatment-related cytopenias (17.6%), disease progression (14.7%), Richter's transformation (11.8%), autoimmune hemolytic anemia (5.9%), diarrhea (2.9%) and infections (8.8%). In one case treatment discontinuation was due to consent withdrawal and one patient was lost to follow-up. The following adverse events of VEN-R treatment were reported during the study: all grade neutropenia (71.8% with grade 3/4 in 55.6%), anemia (51.3%), thrombocytopenia (47%), pneumonia (9.4%), neutropenic fever (6.8%), autoimmune hemolytic anemia (4.3%), immune thrombocytopenic purpura (1.7%), diarrhea (4.3%) and in one case exacerbation of heart failure was observed. Summary/Conclusion: In this retrospective analysis the outcomes of treatment with the VEN-R regimen in real-life setting were worse than those reported in the MURANO trial.
RESUMO
Introduction: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic. The clinical course of COVID-19 was reported to be more severe in patients with cancer, especially with hematological malignancies. Due to the impairment of the immune system, infections are the leading cause of death in patients with chronic lymphocytic leukemia (CLL). Methods: We performed an observational, retrospective study in polish hematological centers within the Polish Adult Leukemia Study Group analyzing the clinical course of SARSCoV- 2 infection in patients with CLL. Results and conclusions: The study group included 188 patients. The median age of the patients was 67.9 years (range 36-87) and 70 (37.2%) were men. The Median Eastern Cooperative Study Group (ECOG) score was 1 (range 0-4). At the time of SARS-CoV-2 infection, 29 (15.4%) patients were treatment-naïve, 41 (21.8%) have ended the treatment, whereas 118 (62.8%) were during the active phase of CLL therapy. The median number of lines of previous treatment regimens was 1 (range 0-7), whereas 24 (12.8%) patients received four or more treatment regimens. At the time of infection 51 patients (27.1%) were treated with Bruton's tyrosine kinase inhibitor (iBTK), 46 (24.5%) with anti-CD20 antibodies while 37 patients (19.7%) were during venetoclax therapy. In the analyzed cohort 111 patients (59.0%) required hospitalization and 50 patients (26.5%) died due to COVID- 19. Patients with poor performance status (ECOG >1), advanced age (≥65 years), low platelet count (<100 G/l), low hemoglobin levels (<10 g/dl), and elevated lactate dehydrogenase (LDH) were at increased risk of death due to SARSCoV- 2 infection. Poor performance status, low platelet count and hemoglobin levels, elevated LDH and advanced Binet stage at diagnosis were associated with the need for hospitalization for the purpose of COVID-19 treatment. Multivariate analysis revealed that independent factors associated with risk of hospitalization due to SARS-CoV-2 infection and its complications were presence of 17p deletion (p = 0.042), anti- CD20 antibody treatment (p = 0.01), low hemoglobin (p = 0.008) and platelet (p = 0.004) levels and elevated LDH (p = 0.0023). Interestingly, the CLL treatment status (treatment naïve vs. treated) or type of administered treatment (BTKi, anti-CD20, or venetoclax) had no impact on SARS-CoV-2 related risk of death. Univariate survival analysis showed that poor performance status (p = 0.02), advanced age (p = 0.04), low platelet count (p = 0.0012), low hemoglobin level (p = 0.0017) and elevated lactate dehydrogenase (p = 0.008) were associated with significantly shorter overall survival. Multivariate Cox regression analysis showed that only the low platelet count (p < 0.0001) and advanced age (p = 0.019) were associated with patients' shorter overall survival. Considering the abovementioned data, SARS-CoV-2 infection in patients with CLL is associated with the poor outcome regardless of administered CLL-directed treatment.
RESUMO
Infections are still one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper was the presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation with Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing (European Conference on Infections in Leukemia (ECIL) and European Society of Blood and Marrow Transplantation (EBMT) guidelines, as well as the results of a survey performed among all Polish transplant centers, were the background material for the working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on the principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.
RESUMO
Introduction: Obinutuzumab-based induction immunochemotherapy was demonstrated to improve the outcome of patients with follicular lymphoma (FL) comparing to the regimens with rituximab in GALLIUM study (NCT01332968). The infusion related reactions (IRRs) occur in more than half of FL patients during the first obinutuzumab administration. Therefore, during the whole treatment period infusions lasting more than 3-4 hours are so far recommended. Shorter infusions would be more convenient for both patients and medical staff and could also contribute to the shorter hospitalization that is desirable during COVID-19 pandemic. The aim of the study was to evaluate the tolerance and early efficacy of obinutuzumab-based regimens in FL patients in clinical practice. Methods: We evaluated tolerability of obinutuzumab infusions and response rates to different regimens of chemotherapy combined with obinutuzumab in consecutive FL patients treated in hemato-oncology centers in Poland from Jan 2020 to Jan 2021. Obinutuzumab was combined with CHOP, CVP or bendamustine according to the treating physician choice. Obinutuzumab maintenance was offered to the patients who achieved at least partial response (PR) after induction immunochemotherapy. Response was evaluated with computed tomography or positron emission tomography according to 2014 Lugano criteria. Adverse events were assessed according to Common Toxicity Criteria (version 5). Results: The study group included 129 treatment-naive FL patients. The median age (range) was 52 (29 - 90) years, 35.7% of patients were males. According to FLIPI 46.5 % of patients were classified as high risk, 33.3% as intermediate and 20.2% as low risk, whereas 33.7%, 30.4% and 35.9% of patients were in PRIMA PI high, intermediate and low risk groups, respectively, Table 1. Median number of GELF criteria was 2 (range 1-6). Induction chemotherapy included: CVP in 48.1% (n=62), CHOP in 29.5% (n=38) and Benda in 22.5% (n=29) of patients. Median number of cycles was 6 (range 1 - 8). Maintenance was started in 85 patients (76.6%). The first obinutuzumab dose was administered as a single infusion during the first day of the first cycle in 43.4% of patients (n=56), whereas 56.6 % (n=73) of patients had initial infusion divided into 2 days (100 mg and 900 mg). During the first cycle 93.8% (n=121) of patients received three doses of obinutuzumab. The doses were omitted in 8 patients: in 4 due to Covid-19, in 1 due to pneumonia and neutropenia and in 3 cases due to neutropenia. IRRs were reported during the first Obinutuzumab administration in 10.1% of patients (n=13, grade 1/2 in 11 and grade 3 in 2 patients): in 7 patients who received obinutuzumab initial dose in single infusion and in 6 patients who received first obinutuzumab dose divided in two days. Median time of the first infusions was 4 hours and 55 min (range 1:30 - 9:45). There were no IRRs reported during the subsequent obinutuzumab infusions. The most common adverse event was neutropenia with grade 3/4 events reported in 51.1% of patients (n=66). G-CSF support was given in 70.4% (n = 81/115), and as the primary prophylaxis in 42.6 % (n=49) of patients. The SARS-CoV-2 infection occurred in 19 patients regardless of initial chemotherapy regimen. After induction immunochemotherapy complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) rates were: 71.8%, 23.9%, 0.9% and 3.4%, respectively, Table 2. With a median follow up of 8.7 months 5 patients (3.9%) relapsed, 4 died due to COVID infection. There were no deaths caused by FL. Conclusions: In our study obinutuzumab-based induction treatment was well tolerated. The low incidence and low grade of infusion related reactions in most of the patients, reported only during the first infusion, support the practice of administration of the first obinutuzumab dose in a single infusion. For convenience, the concept of short, 90 minutes infusion of Obinutuzumab starting from the second cycle could be considered (Canales MA, EHA 2021). During COVID-19 pandemic using obinutu umab with chemotherapy is feasible and justified by the high response rate to this treatment. [Formula presented] Disclosures: Paszkiewicz-Kozik: Roche: Honoraria, Other: congress fee;Servier: Other: congress fee;gillead: Other: travel grant;Takeda: Honoraria, Other: Travel Grants. Hus: Astra Zeneca: Honoraria, Research Funding;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Roche: 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;Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees. Romejko-Jarosinska: roche: Other: congress fee;servier: Other: congress fee;gilead: Other: traver grant. Drozd-Sokolowska: AbbVie: 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;Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka: Janssen: Consultancy, Research Funding;Roche: Consultancy, Research Funding, Speakers Bureau;Servier: Consultancy, Speakers Bureau;Acerta Pharma: Research Funding;AbbVie: Research Funding;Macrogenics: Research Funding;Beigene: Research Funding;MEI Pharma: Research Funding;Incyte Corp.: Research Funding;Takeda: Research Funding. Lech-Marańda: Amgen: Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;Novartis: 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;Roche: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees. Walewski: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Amgen: Consultancy, Honoraria;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS: Consultancy, Honoraria;Celgene: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Servier: Consultancy, Honoraria.
RESUMO
Background: Acute myeloid leukemia (AML) is driven by aberrant leukemic stem cells (LSCs) that initiate and sustain malignancy. To circumvent resistance to therapy, combination therapies with additive mechanisms of action are needed. CD70, a tumor necrosis factor receptor ligand, and its receptor CD27 are expressed on LSCs and AML blasts, but not on hematopoietic stem cells. Cusatuzumab, a high-affinity humanized monoclonal anti-CD70 antibody, kills CD70-expressing cells by Fc domain-mediated effector functions and is a potent inhibitor of CD70-CD27 signaling. Here we report initial results of a study of cusatuzumab in combination with the current standard of care therapy, venetoclax plus azacitidine (CVA), in patients with untreated AML (de novo or secondary) ineligible for intensive chemotherapy due to age ≥75 years or medical comorbidities. Methods: The primary objective of this open label, multicenter, phase 1b study was to assess safety and tolerability of CVA. Key secondary objectives included response rate per ELN 2017 criteria and time to response. Patients received cusatuzumab 10 or 20 mg/kg IV on Day 3 and Day 17, a 3-day ramp-up of venetoclax (100, 200, and 400 mg PO) followed by 400 mg daily dosing, and azacitidine 75 mg/m 2 SC or IV on Days 1-7 of each 28-day cycle. Results: Based on data through Jul 9, 2021, 44 patients enrolled with median age 75 years (range 32-89), 36.4% had secondary AML, 40.9% had an ECOG performance status of 2, and ELN risk was favorable, intermediate and adverse in 18.2%, 20.5% and 61.4%, respectively. All patients received 20 mg/kg cusatuzumab except for 3 patients who received a starting dose of 10 mg/kg with the option to escalate to 20 mg/kg. Of these 3 patients, 1 escalated to 20 mg/kg. At a median follow-up of 29.1 weeks, the median number of treatment cycles was 4.0 (range 1.0-11.0). Grade 3 or above TEAEs were reported in 97.7% of patients;the most common (reported in ≥10%) were neutropenia (68.2%), thrombocytopenia (65.9%), febrile neutropenia (36.4%), anemia (34.1%), leukopenia (29.5%), sepsis (27.3%), and lymphopenia (15.9%). Treatment-emergent serious adverse events (SAEs) were reported in 75% of patients;the most common (reported in at least ≥5%) were febrile neutropenia (27.3%), sepsis (22.7%), COVID-19 (6.8%), and thrombocytopenia (6.8%). Treatment-emergent SAEs of grade ≥3 were reported in 72.7% of the patients. Infusion-related reactions (IRRs) were reported for 11.4% of patients with 2.3% at grade ≥3. Six (13.6%) patients discontinued treatment due to AEs, and 5 (11.4%) TEAEs resulted in death. The mortality rate within 30 days from start of treatment was 4.5%. Table 1 summarizes best response to study treatment. In the intent-to-treat analysis set (n=44) complete remission (CR) rate was 45.5%, while CR + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi) was 77.3%;MLFS was observed in 11.4% of patients. Of 34 responders (defined as CR, CRi or CRh), 47% were MRD negative by flow cytometry at or after achievement of response. Median time to first response for patients who achieved CR, CRh or CRi was 4.21 (3.0-25.0) weeks. Best response rates in the post-hoc response evaluable analysis set (n=42) that excluded two patients who died before the first disease evaluation were: CR in 47.6%, CR + CRh + CRi in 81.0% and MLFS in 11.9% of patients (Table 1). The majority (97.1%) of responders experienced at least one cycle delay in administration of CVA post response. Conclusions: Cusatuzumab administered in combination with venetoclax and azacitidine to elderly patients with untreated AML was generally well tolerated and demonstrated a safety profile consistent with that previously reported with venetoclax-azacitidine, with the addition of generally manageable IRRs. Response rates support an additive effect of cusatuzumab to the standard of care with potential for improved clinical outcomes. However, further clinical trials are needed for validation of these initial results. HK and GB contributed equally to this publ cation. [Formula presented] Disclosures: Roboz: AstraZeneca: Consultancy;Janssen: Research Funding;Bristol Myers Squibb: Consultancy;Jasper Therapeutics: Consultancy;Agios: Consultancy;Novartis: Consultancy;Amgen: Consultancy;Blueprint Medicines: Consultancy;Janssen: Consultancy;Helsinn: Consultancy;Daiichi Sankyo: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Jazz: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Mesoblast: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Astex: Consultancy;Bayer: Consultancy;Astellas: Consultancy;Roche/Genentech: Consultancy;Pfizer: Consultancy;Otsuka: Consultancy. Aribi: Seagen: Consultancy. Brandwein: Astellas: Honoraria;Jazz: Honoraria;Amgen: Honoraria;Taiho: Honoraria;BMS/Celgene: Honoraria;Pfizer: Honoraria;Abbvie: Honoraria;University of Alberta: Current Employment. Döhner: Astellas: Consultancy, Honoraria, Research Funding;AstraZeneca: Consultancy, Honoraria;Berlin-Chemie: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria, Research Funding;Agios: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;GEMoaB: Consultancy, Honoraria;Helsinn: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Jazz: Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding;Oxford Biomedicals: Consultancy, Honoraria;Pfizer: Research Funding;Roche: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding;Astex: Consultancy, Honoraria;Ulm University Hospital: Current Employment. Fiedler: Jazz Pharmaceuticals: Consultancy, Other: support for meeting attendance;Abbvie: Consultancy, Honoraria;Morphosys: Consultancy;Celgene: Consultancy;Pfizer: Consultancy, Research Funding;Novartis: Consultancy;ARIAD/Incyte: Consultancy;Amgen: Consultancy, Other: support for meeting attendance, Patents & Royalties, Research Funding;Servier: Consultancy, Other: support for meeting attendance;Daiichi Sankyo: Consultancy, Other: support for meeting attendance;Stemline: Consultancy. Gandini: argenx: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Geddes: University of Calgary: Current Employment;Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy;Paladin: Consultancy;Janssen: Research Funding;Geron: Research Funding;Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hou: University of Pittsburgh Medical Center Hillman Cancer Centers: Current Employment;AbbVie: Honoraria;AstraZeneca: Honoraria;Karyopharm: Honoraria;Chinese American Hematology Oncology Network: Membership on an entity's Board of Directors or advisory committees. Howes: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Hultberg: argenx: Current Employment, Patents & Royalties. Huselton: University of Rochester: Current Employment. Jacobs: Argenx BV: Current Employment, Current equity holder in publicly-traded company;University of Antwerp: Ended employment in the past 24 months. Kane: Janssen R&D, part of Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Lech-Marańda: Takeda: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors r advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees;Sanofi: 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. Louwers: argenx: Current Employment, Patents & Royalties: Patents (no royalties). Nottage: Janssen R&D, part of Johnson & Johnson: Current Employment;Johnson & Johnson: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Platzbecker: Novartis: Honoraria;AbbVie: Honoraria;Janssen: Honoraria;Celgene/BMS: Honoraria;Geron: Honoraria;Takeda: Honoraria. Rampal: Pharmaessentia: Consultancy;BMS/Celgene: Consultancy;Abbvie: Consultancy;Sierra Oncology: Consultancy;Incyte: Consultancy, Research Funding;Blueprint: Consultancy;Disc Medicine: Consultancy;Jazz Pharmaceuticals: Consultancy;Constellation: Research Funding;Kartos: Consultancy;Stemline: Consultancy, Research Funding;CTI: Consultancy;Novartis: Consultancy;Memorial Sloan Kettering: Current Employment. Salman: Janssen: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Shah: Janssen R&D, part of Johnson & Johnson: Current Employment. Stuart: Clinical Drug Development Consultants LLC: Current Employment;Argenx: Consultancy;Cleave Therapeutics: Consultancy;Triphase Accelerator Corp: Consultancy;IgM Biosciences: Consultancy;Revolution Medicines: Consultancy;Jiya Corp:Consultancy;Geron Corp: Current holder of individual stocks in a privately-held company. Subklewe: Janssen: Consultancy;Pfizer: Consultancy, Speakers Bureau;Takeda: Speakers Bureau;Klinikum der Universität München: Current Employment;MorphoSys: Research Funding;Novartis: Consultancy, Research Funding, Speakers Bureau;Roche: Research Funding;Seattle Genetics: Consultancy, Research Funding;Miltenyi: Research Funding;Gilead: Consultancy, Research Funding, Speakers Bureau;Amgen: Consultancy, Research Funding, Speakers Bureau;BMS/Celgene: Consultancy, Research Funding, Speakers Bureau. Sumbul: argenx: Current Employment. Wang: Takeda: Consultancy, Honoraria, Other: Advisory board;Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board;GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board;Genentech: Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Consultancy, Speakers Bureau;Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau;Novartis: Consultancy, Honoraria, Other: Advisory Board;Mana Therapeutics: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau;Rafael Pharmaceuticals: Other: Data safety monitoring committee;Gilead: Consultancy, Honoraria, Other: Advisory board;Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board;PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board;Genentech: Consultancy;MacroGenics: Consultancy. Wierzbowska: Jazz: Research Funding;Pfizer: Honoraria;Janssen: 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;Astellas: Honoraria, Membership on an entity's Board of Directors or advisory comm ttees;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS: Honoraria. Yao: Statagize LLC: Current Employment;Puma Biotechnology, Inc.: Ended employment in the past 24 months;Argenx: Consultancy. Yee: Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen: Research Funding;TaiHo: Membership on an entity's Board of Directors or advisory committees;Otsuka: Membership on an entity's Board of Directors or advisory committees;Onconova: Research Funding;Pfizer: Membership on an entity's Board of Directors or advisory committees;Tolero: Research Funding;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Paladin: Membership on an entity's Board of Directors or advisory committees;MedImmune: Research Funding;AbbVie: Honoraria;Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees;Forma Therapeutics: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees;Geron: Research Funding;Genentech: Research Funding;F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Jazz: Research Funding. Kantarjian: Immunogen: Research Funding;Astra Zeneca: Honoraria;KAHR Medical Ltd: Honoraria;Astellas Health: Honoraria;Pfizer: Honoraria, Research Funding;NOVA Research: Honoraria;Ascentage: Research Funding;Precision Biosciences: Honoraria;Novartis: Honoraria, Research Funding;Aptitude Health: Honoraria;Ipsen Pharmaceuticals: Honoraria;Jazz: Research Funding;Daiichi-Sankyo: Research Funding;BMS: Research Funding;Amgen: Honoraria, Research Funding;AbbVie: Honoraria, Research Funding;Taiho Pharmaceutical Canada: Honoraria. Borthakur: Protagonist: Consultancy;Ryvu: Research Funding;Astex: Research Funding;GSK: Consultancy;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;University of Texas MD Anderson Cancer Center: Current Employment;ArgenX: Membership on an entity's Board of Directors or advisory committees.
RESUMO
Background: Adult patients (pts) with secondary immunodeficiency in the course of blood cancers are at risk of severe COVID-19 with an unprecedented 34% risk of death. So far, no standards have been established to manage pts with hematological malignancies (HM) infected with SARS-CoV-2. Rapid control of SARS-COV-2 infection and the prevention of its complicated course are essential for clinical management, especially in those pts who require urgent systemic anti-cancer therapy (SACT). The treatment with remdesivir, dexamethasone and convalescent plasma have been shown to be active in COVID-19 treatment. Aims: Here we present our experience with the use of these agents in a difficult-to-treat population with various HM (in particular aggressive lymphomas, acute leukemias and progressive indolent lymphomas) whose SACT has been disrupted due to active SARS-CoV-2 infection. Methods: The observational, single-centre study was conducted from 07 November 2020 to 26 February 2021. All pts were diagnosed with HM and active SARS-CoV-2 infection requiring hospitalization. The severity of COVID-19 was evaluated according to the World Health Organization (WHO) Clinical Progression Scale. The COVID-19 directed treatment included remdesivir (at the standard dose for 5 consecutive days), COVID-19 convalescent plasma transfusion and dexamethasone. All patients gave their written informed consent for the data collection, and ethical clearance was obtained from the Ethics Committee of the Institute of Hematology and Transfusion Medicine, Warsaw, Poland. Results: At the time of analysis thirty-six pts were included. The median age at COVID-19 diagnosis was 58.5 years (23-86), with male predominance (21 men and 15 women). All pts were diagnosed with HM: 11 pts with acute myeloid leukemia (30.5%), 3 pts with acute lymphoblastic leukemia (8.3%), 6 pts with mantle cell lymphoma (16.7%), 5 pts with chronic lymphocytic leukemia (13.9%), 2 pts with chronic myeloid leukemia (5.5%) and 2 pts with myelodysplastic syndrome (5.5%). The COVID-19 was diagnosed before and during treatment for underlying HM in 5 and 30 pts, respectively. At the time of COVID-19 diagnosis, median WBC was 3.5 G/L (0.05-165), median ANC for myeloid and lymphoid disease were 0.19 G/L (0.0 - 6.3) and 2.3 G/L (0.7-27), respectively. The median serum concentration of hemoglobin and PLT count was 9.2 g/dL (5.4-14.3) and 91 (4-800), respectively. The maximum severity of COVID-19 according to the WHO score was as follows: 4, 5-6, ≥ 7 points in 36%, 42% and 22% of pts, respectively. All pts received remdesivir with dexamethasone. The convalescent plasma transfusion was applied to 21 pts (57%). There were no transfusion related adverse events. The median time of hospitalization was 19.5 days (4-59). In total, 8 pts (22%) died;7 due to COVID-19 and 1 due to progressive HM. SACT was initiated in all COVID-19 survivors requiring treatment with the median time of 17 days (9-65). Summary/Conclusion: Treatment with remdesivir, dexamethasone and COVID-19 convalescent plasma transfusion may improve outcomes of adult HM patients infected with SARS-CoV-2 and provide the benefit of early initiation of systemic anti-cancer therapy.