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<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> &lt; 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>

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Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月4日

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  • 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

摘要

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.