A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma.

Abstract

To report the activity of venetoclax in patients with relapsed mantle cell lymphoma (MCL), we identified 81 patients treated with venetoclax monotherapy (n = 50, 62%) or in combination with a Bruton tyrosine kinase inhibitor (BTKi) (n = 16, 20%), an anti-CD20 monoclonal antibody (n = 11, 14%), or other active agents at 12 US academic medical centers. Patients had high-risk disease features including Ki67 >30% (61%), blastoid/pleomorphic histology (29%), complex karyotype (34%), and TP53 alterations (49%), and received a median of 3 prior treatments including BTKis in 91%. Venetoclax alone or in combination resulted in an overall response rate (ORR) of 40% and median progression-free (PFS) and overall survival (OS) of 3.7 and 12.5 months, respectively. The receipt of ≤3 prior treatments was associated with higher odds of response to venetoclax in a univariable analysis. In a multivariable analysis, having a high-risk Mantle Cell Lymphoma International Prognostic Index score before receiving venetoclax and disease relapse or progression within 24 months of diagnosis were associated with inferior OS whereas the use of venetoclax in combination was associated with superior OS. Although most patients (61%) had low risk for tumor lysis syndrome (TLS), 12.3% of patients developed TLS despite the implementation of several mitigation strategies. In conclusion, venetoclax resulted in good ORR but short PFS in patients with MCL who are at high risk, and may have a better role in earlier lines of treatment and/or in conation with other active agents. TLS remains an important risk in patients with MCL who initiate treatment with venetoclax.

• Authors: Yazeed Sawalha, Subir Goyal, Jeffrey M Switchenko, Jason T Romancik, Manali Kamdar, I Brian Greenwell, Brian T Hess, Krista M Isaac, Craig A Portell, Alex Mejia Garcia, Scott Goldsmith, Natalie S Grover, Peter A Riedell, Reem Karmali, Madelyn Burkart, Michael Buege, Othman Akhtar, Pallawi Torka, Anita Kumar, Brian T Hill, Brad S Kahl, Jonathon B Cohen
• Journal: Blood advances (Blood Adv) Vol. 7 Issue 13 Pg. 2983-2993 (07 11 2023) ISSN: 2473-9537 [Electronic] United States
• PMID: 36809796 (Publication Type: Multicenter Study, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• venetoclax
• Antineoplastic Agents
• Bridged Bicyclo Compounds, Heterocyclic

Topics

• Humans
• Adult
• Lymphoma, Mantle-Cell (drug therapy)
• Neoplasm Recurrence, Local
• Antineoplastic Agents (adverse effects)
• Bridged Bicyclo Compounds, Heterocyclic (therapeutic use)
• Tumor Lysis Syndrome