Abiola Bolarinwa, Madhu Nagaraj, Saurabh Zanwar, Nadine Abdallah, P. Leif Bergsagel, Moritz Binder, Francis Buadi, Saurabh Chhabra, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A. Gertz, Wilson Gonsalves, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Ricardo Parrondo, Vivek Roy, Taimur Sher, Mustaqeem Siddiqui, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Udit Yadav, J. Erin Wiedmeier-Nutor, Linda B. Baughn, S. Vincent Rajkumar, Rafael Fonseca, Sikander Ailawadhi, Shaji Kumar
{"title":"基于venetoclax的复发/难治性多发性骨髓瘤联合治疗：实践模式和继发性细胞遗传学异常对结果的影响","authors":"Abiola Bolarinwa, Madhu Nagaraj, Saurabh Zanwar, Nadine Abdallah, P. Leif Bergsagel, Moritz Binder, Francis Buadi, Saurabh Chhabra, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A. Gertz, Wilson Gonsalves, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Ricardo Parrondo, Vivek Roy, Taimur Sher, Mustaqeem Siddiqui, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Udit Yadav, J. Erin Wiedmeier-Nutor, Linda B. Baughn, S. Vincent Rajkumar, Rafael Fonseca, Sikander Ailawadhi, Shaji Kumar","doi":"10.1038/s41408-025-01264-2","DOIUrl":null,"url":null,"abstract":"<p>Venetoclax (Ven), a BCL-2 inhibitor, has demonstrated efficacy in patients with relapsed/refractory multiple myeloma (RRMM) harboring a t(11;14) and/or elevated BCL-2 expression. However, data from clinical trial remain inconclusive. This retrospective study evaluated the efficacy and safety of Ven-based therapies in 232 MM patients without concurrent AL amyloidosis treated at Mayo Clinic sites between Jan 2015 and Dec 2023. The median age was 62 years, with a median of 3 prior lines of therapy. Among the cohort, 82% had t(11;14), and elevated BCL-2 expression was identified in 17 of 18 non-t(11;14) patients tested. Ven combinations included Ven-Dex (VenD; 48.3%), Proteasome Inhibitor-Ven (30.2%), and Daratumumab-Ven (19%) with other combinations making up the rest. The overall response rate was 57%; 64% for t(11;14) patients and 26% for non-t(11;14) patients. Median progression-free survival (PFS) was 9.4 months overall; 11.8 months for t(11;14) patients and 2.9 months for those without (<i>p</i> < 0.001). Among t(11;14) patients, the presence of del(17p) or 1q gain/amplification significantly reduced PFS to 7.7 months. Venetoclax-based regimens remain an important option for t(11;14) patients, but efficacy is limited in patients without a t(11;14). The presence of secondary high-risk cytogenetics imparts an inferior PFS.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"141 1","pages":""},"PeriodicalIF":12.9000,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes\",\"authors\":\"Abiola Bolarinwa, Madhu Nagaraj, Saurabh Zanwar, Nadine Abdallah, P. Leif Bergsagel, Moritz Binder, Francis Buadi, Saurabh Chhabra, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A. Gertz, Wilson Gonsalves, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Ricardo Parrondo, Vivek Roy, Taimur Sher, Mustaqeem Siddiqui, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Udit Yadav, J. Erin Wiedmeier-Nutor, Linda B. Baughn, S. Vincent Rajkumar, Rafael Fonseca, Sikander Ailawadhi, Shaji Kumar\",\"doi\":\"10.1038/s41408-025-01264-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Venetoclax (Ven), a BCL-2 inhibitor, has demonstrated efficacy in patients with relapsed/refractory multiple myeloma (RRMM) harboring a t(11;14) and/or elevated BCL-2 expression. However, data from clinical trial remain inconclusive. This retrospective study evaluated the efficacy and safety of Ven-based therapies in 232 MM patients without concurrent AL amyloidosis treated at Mayo Clinic sites between Jan 2015 and Dec 2023. The median age was 62 years, with a median of 3 prior lines of therapy. Among the cohort, 82% had t(11;14), and elevated BCL-2 expression was identified in 17 of 18 non-t(11;14) patients tested. Ven combinations included Ven-Dex (VenD; 48.3%), Proteasome Inhibitor-Ven (30.2%), and Daratumumab-Ven (19%) with other combinations making up the rest. The overall response rate was 57%; 64% for t(11;14) patients and 26% for non-t(11;14) patients. Median progression-free survival (PFS) was 9.4 months overall; 11.8 months for t(11;14) patients and 2.9 months for those without (<i>p</i> < 0.001). Among t(11;14) patients, the presence of del(17p) or 1q gain/amplification significantly reduced PFS to 7.7 months. Venetoclax-based regimens remain an important option for t(11;14) patients, but efficacy is limited in patients without a t(11;14). The presence of secondary high-risk cytogenetics imparts an inferior PFS.</p>\",\"PeriodicalId\":8989,\"journal\":{\"name\":\"Blood Cancer Journal\",\"volume\":\"141 1\",\"pages\":\"\"},\"PeriodicalIF\":12.9000,\"publicationDate\":\"2025-04-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Blood Cancer Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41408-025-01264-2\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Cancer Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41408-025-01264-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes
Venetoclax (Ven), a BCL-2 inhibitor, has demonstrated efficacy in patients with relapsed/refractory multiple myeloma (RRMM) harboring a t(11;14) and/or elevated BCL-2 expression. However, data from clinical trial remain inconclusive. This retrospective study evaluated the efficacy and safety of Ven-based therapies in 232 MM patients without concurrent AL amyloidosis treated at Mayo Clinic sites between Jan 2015 and Dec 2023. The median age was 62 years, with a median of 3 prior lines of therapy. Among the cohort, 82% had t(11;14), and elevated BCL-2 expression was identified in 17 of 18 non-t(11;14) patients tested. Ven combinations included Ven-Dex (VenD; 48.3%), Proteasome Inhibitor-Ven (30.2%), and Daratumumab-Ven (19%) with other combinations making up the rest. The overall response rate was 57%; 64% for t(11;14) patients and 26% for non-t(11;14) patients. Median progression-free survival (PFS) was 9.4 months overall; 11.8 months for t(11;14) patients and 2.9 months for those without (p < 0.001). Among t(11;14) patients, the presence of del(17p) or 1q gain/amplification significantly reduced PFS to 7.7 months. Venetoclax-based regimens remain an important option for t(11;14) patients, but efficacy is limited in patients without a t(11;14). The presence of secondary high-risk cytogenetics imparts an inferior PFS.
期刊介绍：
Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as:
Preclinical studies of new compounds, especially those that provide mechanistic insights
Clinical trials and observations
Reviews related to new drugs and current management of hematologic malignancies
Novel observations related to new mutations, molecular pathways, and tumor genomics
Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.
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