M. Brocard, D. Roos-Weil, L. Kanagaratnam, L. Bussot, B. Papoular, C. Tomowiak, S. Chevreux, G. Crochet, T. Vaugeois, E. Toussaint, A. Quinquenel, P. Kapoor, E. Durot
{"title":"CD3XCD20 BISPECIFIC ANTIBODIES IN TRANSFORMED WALDENSTRÖM MACROGLOBULINEMIA/LYMPHOPLASMACYTIC LYMPHOMA","authors":"M. Brocard, D. Roos-Weil, L. Kanagaratnam, L. Bussot, B. Papoular, C. Tomowiak, S. Chevreux, G. Crochet, T. Vaugeois, E. Toussaint, A. Quinquenel, P. Kapoor, E. Durot","doi":"10.1002/hon.70094_264","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> Patients with histological transformation (HT) of Waldenström macroglobulinemia (WM) who relapse or are refractory (R/R) have a poor prognosis, especially those who are not eligible or relapsing after high-dose chemotherapy with autologous stem cell transplant (ASCT) and/or chimeric antigen receptor (CAR) T-cell therapy. CD3xCD20 bispecific monoclonal antibodies (BsAb) (epcoritamab, glofitamab) provide overall and complete responses of around 60% and 40%, respectively, in R/R diffuse large-cell B lymphomas (DLBCL). However, these therapies have not been evaluated in HT of WM. The aim of this study was to evaluate the efficacy and safety of CD3xCD20 BsAb in patients with R/R transformed WM.</p><p><b>Methods:</b> We retrospectively identified patients with biopsy-proven transformed WM/lymphoplasmacytic lymphoma treated with epcoritamab or glofitamab in FILO/LYSA centers and an American center. The primary endpoint was best overall response rate (ORR). Secondary endpoints were best complete response rate (CRR), progression free-survival (PFS), overall survival (OS) and safety. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to the ASTCT 2019 criteria. Hematological toxicity and infections were graded according to NCI CTCAE (version 5.0).</p><p><b>Results:</b> Between February 2023 and July 2024, 12 patients with R/R transformed WM were treated with BsAb (6 glofitamab and 6 epcoritamab). Median age at WM diagnosis was 72 years (range 43–83). Patients received a median of 1 prior line of treatment (range, 0–6) for WM, including 4 treated with a BTK inhibitor (2 with ibrutinib, 1 with zanubritinib and 1 received both successively). 4 patients had concurrent diagnosis of WM and DLBCL. For the others, the median time from WM to HT was 5.3 years (range, 0.4–12.8) and 15 months (range, 1–48) from HT diagnosis to BsAb. Patients had received a median of 2 prior lines (range, 1–5) for HT. Five patients were previously treated with CAR T-cell, including 2 with prior ASCT. At the time of BsAb, 75% of patients were refractory to the last treatment, and 67% to at least 2 consecutive lines. The median age was 80 years (range, 45–86). Patient treated with glofitamab had received a median of 9 cycles (6–12) and those treated with epcoritamab a median of 3 cycles (2–6). Best ORR was 92% and best CRR was 42%. CRS occurred in 10 patients (83%, with only 1 grade 3) and ICANS in 2 patients (17%, no grade 3–4). Seven patients (58%) presented infections, including 4 grade 3. After a median follow-up of 9.4 months (95% CI: 4–23), the 6-months PFS and OS were 57% (95% CI: 34%–94%) and 75% (95% CI: 54%–100%), respectively. Five deaths were reported, 3 due to disease progression and 2 from infection.</p><p><b>Conclusion:</b> This study shows an interesting efficacy of CD3xCD20 BsAb in R/R transformed WM in a population of elderly and heavily pre-treated patients, without unexpected toxicity.</p><p><b>Keywords:</b> aggressive B-cell non-Hodgkin lymphoma; immunotherapy</p><p><b>Potential sources of conflict of interest:</b></p><p><b>G. Crochet</b></p><p><b>Honoraria:</b> Roche, Abbvie, Kite/Gilead, BMS, Sobbi</p><p><b>Educational</b> <b>grants:</b> Roche, Abbvie, Kite/Gilead, BMS, Sobbi</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_264","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70094_264","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Patients with histological transformation (HT) of Waldenström macroglobulinemia (WM) who relapse or are refractory (R/R) have a poor prognosis, especially those who are not eligible or relapsing after high-dose chemotherapy with autologous stem cell transplant (ASCT) and/or chimeric antigen receptor (CAR) T-cell therapy. CD3xCD20 bispecific monoclonal antibodies (BsAb) (epcoritamab, glofitamab) provide overall and complete responses of around 60% and 40%, respectively, in R/R diffuse large-cell B lymphomas (DLBCL). However, these therapies have not been evaluated in HT of WM. The aim of this study was to evaluate the efficacy and safety of CD3xCD20 BsAb in patients with R/R transformed WM.
Methods: We retrospectively identified patients with biopsy-proven transformed WM/lymphoplasmacytic lymphoma treated with epcoritamab or glofitamab in FILO/LYSA centers and an American center. The primary endpoint was best overall response rate (ORR). Secondary endpoints were best complete response rate (CRR), progression free-survival (PFS), overall survival (OS) and safety. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to the ASTCT 2019 criteria. Hematological toxicity and infections were graded according to NCI CTCAE (version 5.0).
Results: Between February 2023 and July 2024, 12 patients with R/R transformed WM were treated with BsAb (6 glofitamab and 6 epcoritamab). Median age at WM diagnosis was 72 years (range 43–83). Patients received a median of 1 prior line of treatment (range, 0–6) for WM, including 4 treated with a BTK inhibitor (2 with ibrutinib, 1 with zanubritinib and 1 received both successively). 4 patients had concurrent diagnosis of WM and DLBCL. For the others, the median time from WM to HT was 5.3 years (range, 0.4–12.8) and 15 months (range, 1–48) from HT diagnosis to BsAb. Patients had received a median of 2 prior lines (range, 1–5) for HT. Five patients were previously treated with CAR T-cell, including 2 with prior ASCT. At the time of BsAb, 75% of patients were refractory to the last treatment, and 67% to at least 2 consecutive lines. The median age was 80 years (range, 45–86). Patient treated with glofitamab had received a median of 9 cycles (6–12) and those treated with epcoritamab a median of 3 cycles (2–6). Best ORR was 92% and best CRR was 42%. CRS occurred in 10 patients (83%, with only 1 grade 3) and ICANS in 2 patients (17%, no grade 3–4). Seven patients (58%) presented infections, including 4 grade 3. After a median follow-up of 9.4 months (95% CI: 4–23), the 6-months PFS and OS were 57% (95% CI: 34%–94%) and 75% (95% CI: 54%–100%), respectively. Five deaths were reported, 3 due to disease progression and 2 from infection.
Conclusion: This study shows an interesting efficacy of CD3xCD20 BsAb in R/R transformed WM in a population of elderly and heavily pre-treated patients, without unexpected toxicity.
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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