Pub Date : 2024-09-07DOI: 10.1016/j.clml.2024.08.009
Massimo Breccia, Rosalba Cucci, Giovanni Marsili, Fausto Castagnetti, Sara Galimberti, Barbara Izzo, Federica Sorà, Simona Soverini, Monica Messina, Alfonso Piciocchi, Massimiliano Bonifacio, Daniela Cilloni, Alessandra Iurlo, Giovanni Martinelli, Gianantonio Rosti, Fabio Stagno, Paola Fazi, Marco Vignetti, Fabrizio Pane
Background: In the last decade, TKIs improved the overall survival (OS) of chronic myeloid leukemia (CML) patients who achieved a deep and sustained molecular response (DMR, defined as stable MR4 and MR4.5). Those patients may attempt therapy discontinuation. In our analysis, we report the differences in eligibility criteria due to time of response and different TKI used as frontline treatment analyzed in a large cohort of CP-CML patients.
Methods: Data were exported by LabNet CML, a network founded by GIMEMA in 2014. The network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and molecular residual disease (MRD) monitoring.
Results: Out of 1777 patients analyzed, 774 had all evaluable timepoints (3, 6, and 12 months). At 3 months, 40 patients obtained ≥MR4: of them 14 (3.6%) with imatinib, 8 (5.8%) with dasatinib, and 18 (7.4%) with nilotinib (P = .093); at 6 months, 146 patients were in MR4: 42 (11%) with imatinib, 38 (28%) with dasatinib, and 66 (27%) with nilotinib (P < .001). At 12 months, 231 patients achieved a DMR: 85 (22%) with imatinib, 55 (40%) with dasatinib and 91 (38%) with nilotinib (P < .001). Achieving at least ≥MR2 at 3 months, was predictive of a DMR at any timepoint of observation: with imatinib 67% versus 30% of patients with 2 years was significant for patients who at 3 months had ≥MR2 (18% vs. 9.9% of pts with
Conclusion: In conclusion, reaching ≥MR2 and a MR3 at 3 months it seems predictive of a DMR at any time point. Considering the prerequisite for a discontinuation with a sustained DMR only a minority of patients can be eligible for the discontinuation, regardless the frontline treatment received.
{"title":"Deep Molecular Response Rate in Chronic Phase Chronic Myeloid Leukemia: Eligibility to Discontinuation Related to Time to Response and Different Frontline TKI in the Experience of the Gimema Labnet CML National Network.","authors":"Massimo Breccia, Rosalba Cucci, Giovanni Marsili, Fausto Castagnetti, Sara Galimberti, Barbara Izzo, Federica Sorà, Simona Soverini, Monica Messina, Alfonso Piciocchi, Massimiliano Bonifacio, Daniela Cilloni, Alessandra Iurlo, Giovanni Martinelli, Gianantonio Rosti, Fabio Stagno, Paola Fazi, Marco Vignetti, Fabrizio Pane","doi":"10.1016/j.clml.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.clml.2024.08.009","url":null,"abstract":"<p><strong>Background: </strong>In the last decade, TKIs improved the overall survival (OS) of chronic myeloid leukemia (CML) patients who achieved a deep and sustained molecular response (DMR, defined as stable MR4 and MR4.5). Those patients may attempt therapy discontinuation. In our analysis, we report the differences in eligibility criteria due to time of response and different TKI used as frontline treatment analyzed in a large cohort of CP-CML patients.</p><p><strong>Methods: </strong>Data were exported by LabNet CML, a network founded by GIMEMA in 2014. The network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and molecular residual disease (MRD) monitoring.</p><p><strong>Results: </strong>Out of 1777 patients analyzed, 774 had all evaluable timepoints (3, 6, and 12 months). At 3 months, 40 patients obtained ≥MR4: of them 14 (3.6%) with imatinib, 8 (5.8%) with dasatinib, and 18 (7.4%) with nilotinib (P = .093); at 6 months, 146 patients were in MR4: 42 (11%) with imatinib, 38 (28%) with dasatinib, and 66 (27%) with nilotinib (P < .001). At 12 months, 231 patients achieved a DMR: 85 (22%) with imatinib, 55 (40%) with dasatinib and 91 (38%) with nilotinib (P < .001). Achieving at least ≥MR2 at 3 months, was predictive of a DMR at any timepoint of observation: with imatinib 67% versus 30% of patients with <MR2, with dasatinib 66% versus 28% of patients with <MR2, and with nilotinib 75% versus 30% of patients with < MR2 (P < .001). At the same time point, achieving at least ≥MR3 is even more predictive of a DMR at any timepoint: 89% versus 38% of patients with <MR3 with imatinib (P < .001), 84% versus 40% of patients with <MR3 with dasatinib (P < .001), and 89% versus 49% of patients with <MR3 with nilotinib (P < .001). Of 908 patients who reached a DMR, 461 (51%) lost it: the loss of response after >2 years was significant for patients who at 3 months had ≥MR2 (18% vs. 9.9% of pts with <MR2, P = .038).</p><p><strong>Conclusion: </strong>In conclusion, reaching ≥MR2 and a MR3 at 3 months it seems predictive of a DMR at any time point. Considering the prerequisite for a discontinuation with a sustained DMR only a minority of patients can be eligible for the discontinuation, regardless the frontline treatment received.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.clml.2024.08.010
Michael Schneider, Sunita D Nasta, Stefan K Barta, Elise A Chong, Jakub Svoboda, Stephen J Schuster, Daniel J Landsburg
Background: Large B cell lymphoma (LBCL) is the most common form of lymphoma. Polatuzumab vedotin (polatuzumab) is an effective therapy for patients diagnosed with LBCL; however, only limited information regarding pathologic features detected by clinical laboratory assays is available to determine which patients are most likely to benefit from polatuzumab based therapies.
Patients and methods: We collected data from real world patients with relapsed or refractory LBCL whose tumors underwent next generation sequencing and were treated with polatuzumab based therapy at a single large academic cancer center. Tumor and patient characteristics were analyzed to look for factors that predict response to polatuzumab based therapies.
Results: We identified high grade B cell lymphoma (HGBL) -NOS or MYC/BCL2 histology and presence of MYC rearrangement as factors that predict inferior response to polatuzumab based therapy. Patients with germinal center B cell of origin (GCB COO) LBCL without these factors had a high response rate (73%) to polatuzumab based therapy.
Conclusion: In a single center real world retrospective analysis of R/R LBCL patients with available genomic data, polatuzumab based therapy may be less effective in patients with HGBL-NOS or MYC/BCL2 histology and MYC rearrangements, but not in patients with GCB COO LBCL without these features. Routine performance of more comprehensive pathologic analysis of tumors may inform the use of polatuzumab based therapy in patients with LBCL.
背景：大 B 细胞淋巴瘤（LBCL大B细胞淋巴瘤（LBCL）是最常见的淋巴瘤。Polatuzumab vedotin（泊拉珠单抗）是一种治疗确诊的大B细胞淋巴瘤患者的有效疗法；然而，目前只有临床实验室检测所发现的病理特征方面的有限信息，无法确定哪些患者最有可能从基于泊拉珠单抗的疗法中获益：我们收集了复发性或难治性LBCL患者的真实数据，这些患者的肿瘤接受了新一代测序，并在一家大型学术癌症中心接受了基于泊拉珠单抗的治疗。我们对肿瘤和患者特征进行了分析，以寻找预测对泊拉珠单抗疗法反应的因素：结果：我们发现高级别B细胞淋巴瘤（HGBL）-NOS或MYC/BCL2组织学和MYC重排是预测对泊拉珠单抗疗法反应较差的因素。不存在这些因素的生殖中心B细胞来源（GCB COO）LBCL患者对泊拉珠单抗治疗的反应率较高（73%）：结论：在一项对有基因组数据的R/R LBCL患者进行的单中心真实世界回顾性分析中，基于泊拉珠单抗的治疗对组织学为HGBL-NOS或MYC/BCL2和MYC重排的患者可能效果较差，但对无这些特征的GCB COO LBCL患者则无效。对肿瘤进行更全面的常规病理分析可为LBCL患者使用泊拉珠单抗疗法提供参考。
{"title":"Analysis of Histologic, Immunohistochemical and Genomic Features of Large B Cell Lymphoma Tumors May Predict Response to Polatuzumab Vedotin Based Therapy in Patients With Relapsed/Refractory Disease.","authors":"Michael Schneider, Sunita D Nasta, Stefan K Barta, Elise A Chong, Jakub Svoboda, Stephen J Schuster, Daniel J Landsburg","doi":"10.1016/j.clml.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.clml.2024.08.010","url":null,"abstract":"<p><strong>Background: </strong>Large B cell lymphoma (LBCL) is the most common form of lymphoma. Polatuzumab vedotin (polatuzumab) is an effective therapy for patients diagnosed with LBCL; however, only limited information regarding pathologic features detected by clinical laboratory assays is available to determine which patients are most likely to benefit from polatuzumab based therapies.</p><p><strong>Patients and methods: </strong>We collected data from real world patients with relapsed or refractory LBCL whose tumors underwent next generation sequencing and were treated with polatuzumab based therapy at a single large academic cancer center. Tumor and patient characteristics were analyzed to look for factors that predict response to polatuzumab based therapies.</p><p><strong>Results: </strong>We identified high grade B cell lymphoma (HGBL) -NOS or MYC/BCL2 histology and presence of MYC rearrangement as factors that predict inferior response to polatuzumab based therapy. Patients with germinal center B cell of origin (GCB COO) LBCL without these factors had a high response rate (73%) to polatuzumab based therapy.</p><p><strong>Conclusion: </strong>In a single center real world retrospective analysis of R/R LBCL patients with available genomic data, polatuzumab based therapy may be less effective in patients with HGBL-NOS or MYC/BCL2 histology and MYC rearrangements, but not in patients with GCB COO LBCL without these features. Routine performance of more comprehensive pathologic analysis of tumors may inform the use of polatuzumab based therapy in patients with LBCL.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/S2152-2650(24)01915-3
Bruno Costa, Carlyn Tan, Tala Shekarkhand, Ross Firestone, Eric Jurgens, Kevin Miller, Alexander Lesokhin, Gunjan Shah, Neha Korde, Sridevi Rajeeve, David Chung, Heather Landau, Michael Scordo, Hani Hassoun, Kylee Maclachlan, Urvi Shah, Malin Hultcrantz, Issam Hamadeh, Sergio Giralt, Sham Mailankody, Hamza Hashmi
{"title":"P-012 Real-World Safety and Early Efficacy of Talquetamab in Patients with Heavily-Pretreated Relapsed/Refractory Multiple Myeloma","authors":"Bruno Costa, Carlyn Tan, Tala Shekarkhand, Ross Firestone, Eric Jurgens, Kevin Miller, Alexander Lesokhin, Gunjan Shah, Neha Korde, Sridevi Rajeeve, David Chung, Heather Landau, Michael Scordo, Hani Hassoun, Kylee Maclachlan, Urvi Shah, Malin Hultcrantz, Issam Hamadeh, Sergio Giralt, Sham Mailankody, Hamza Hashmi","doi":"10.1016/S2152-2650(24)01915-3","DOIUrl":"10.1016/S2152-2650(24)01915-3","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"24 ","pages":"Pages S46-S47"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/S2152-2650(24)01900-1
Christopher Parrish, Alexandra Welsh, John Ashcroft, Catherine Olivier, Anna Hockaday, Jamie Cavenagh, John Snowden, Mark Drayson, Ruth De Tute, Roger Owen, Kwee Yong, Mamta Garg, Kevin Boyd, Hamdi Sati, Sharon Gillson, Jeanine Richards, Mark Cook, Lesley Roberts, David Cairns, Gordon Cook
Pub Date : 2024-09-01DOI: 10.1016/S2152-2650(24)01853-6
Andrew Spencer, Marc-Steffen Raab, Shinsuke Iida, María-Victoria Mateos Manteca, Michele Cavo, Paula Rodriguez-Otero, P. Joy Ho, Yunxin Chen, Paul Ferguson, Irit Avivi, Paolo Corradini, Esther Chan, Andy Chen, Bertrand Arnulf, Udo Holtick, Adam Sperling, Jufen Chu, David Pearson, Davide Germano, Ronan Feighery, Nikhil Munshi
{"title":"OA-12 Interim Phase 2 Study Results of Durcabtagene Autoleucel (PHE885), a T-Charge™ Manufactured BCMA-Directed CAR-T Cell Therapy in Patients (pts) with r/r Multiple Myeloma (RRMM)","authors":"Andrew Spencer, Marc-Steffen Raab, Shinsuke Iida, María-Victoria Mateos Manteca, Michele Cavo, Paula Rodriguez-Otero, P. Joy Ho, Yunxin Chen, Paul Ferguson, Irit Avivi, Paolo Corradini, Esther Chan, Andy Chen, Bertrand Arnulf, Udo Holtick, Adam Sperling, Jufen Chu, David Pearson, Davide Germano, Ronan Feighery, Nikhil Munshi","doi":"10.1016/S2152-2650(24)01853-6","DOIUrl":"10.1016/S2152-2650(24)01853-6","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"24 ","pages":"Pages S8-S9"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/S2152-2650(24)01922-0
David Fandrei, Michael Rade, Markus Kreuz, Luise Fischer, Patrick Born, Sabine Seiffert, Andreas Boldt, Jonathan Scolnick, Lakshmi Venkatraman, Stacy Xu, Ronny Baber, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Klaus H. Metzeler, Marco Herling, Madlen Jentzsch, Carmen Herling, Georg-Nikolaus Franke, Ulrike Köhl, Maximilan Merz
{"title":"P-019 Cytotoxic CD4+ T cells are major drivers of side effects and response after chimeric antigen receptor T cells against BCMA","authors":"David Fandrei, Michael Rade, Markus Kreuz, Luise Fischer, Patrick Born, Sabine Seiffert, Andreas Boldt, Jonathan Scolnick, Lakshmi Venkatraman, Stacy Xu, Ronny Baber, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Klaus H. Metzeler, Marco Herling, Madlen Jentzsch, Carmen Herling, Georg-Nikolaus Franke, Ulrike Köhl, Maximilan Merz","doi":"10.1016/S2152-2650(24)01922-0","DOIUrl":"10.1016/S2152-2650(24)01922-0","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"24 ","pages":"Page S51"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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