Advancing the understanding of venetoclax in t(11;14)-positive multiple myeloma: a comprehensive review of clinical evidence and future prospects

References

• Mihalyova J, Jelinek T, Growkova K, et al. Venetoclax: a new wave in hematooncology. Exp Hematol. 2018;61:10–25. doi:10.1016/j.exphem.2018.02.002
   PubMed Web of Science ®Google Scholar
• Paner A, Patel P, Dhakal B. The evolving role of translocation t(11;14) in the biology, prognosis, and management of multiple myeloma. Blood Rev. 2020;41:100643. doi:10.1016/j.blre.2019.100643
   PubMed Web of Science ®Google Scholar
• Roberts AW, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):311–322. doi:10.1056/NEJMoa1513257
   PubMed Web of Science ®Google Scholar
• Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17(6):768–778. doi:10.1016/S1470-2045(16)30019-5
   PubMed Web of Science ®Google Scholar
• Konopleva M, et al. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov. 2016;6(10):1106–1117. doi:10.1158/2159-8290.CD-16-0313
   PubMed Web of Science ®Google Scholar
• Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-hodgkin lymphoma. J Clin Oncol. 2017;35(8):826–833. doi:10.1200/JCO.2016.70.4320
   PubMed Web of Science ®Google Scholar
• Kaufman JL, Gasparetto CJ, Mikhael J, et al. Phase 1 study of venetoclax in combination with dexamethasone as targeted therapy for t(11;14) relapsed/refractory multiple myeloma. Blood. 2017;130(Supplement 1):3131. doi:10.1182/blood.V130.Suppl_1.3131.3131
   Google Scholar
• Kumar S, Kaufman JK, Gasparetto C, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130(22):2401–2409. doi:10.1182/blood-2017-06-788786
   PubMed Web of Science ®Google Scholar
• Moreau P, Chanan-Khan A, Roberts AW, et al. Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM. Blood. 2017;130(22):2392–2400. doi:10.1182/blood-2017-06-788323
   PubMed Web of Science ®Google Scholar
• Costa LJ, Davies FE, Monohan GP, et al. Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. Blood Adv. 2021;5(19):3748–3759. doi:10.1182/bloodadvances.2020004146
   PubMed Web of Science ®Google Scholar
• Kumar SK, Harrison SJ, Cavo M, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2020;21(12):1630–1642. doi:10.1016/S1470-2045(20)30525-8
   PubMed Web of Science ®Google Scholar
• Touzeau C, Dousset C, Le Gouill S, et al. The BCL2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma. Leukemia. 2014;28(1):210–212. doi:10.1038/leu.2013.216
   PubMed Web of Science ®Google Scholar
• Morales AA, Kurtoglu M, Matulis SM, et al. Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/BCL2 in Mcl-1-expressing myeloma cells. Blood. 2011;118(5):1329–1339. doi:10.1182/blood-2011-01-327197
   PubMed Web of Science ®Google Scholar
• Gupta VA, Matulis SM, Conage-Pough JE, et al. Bone marrow microenvironment-derived signals induce Mcl-1 dependence in multiple myeloma. Blood. 2017;129(14):1969–1979. doi:10.1182/blood-2016-10-745059
   PubMed Web of Science ®Google Scholar
• Matulis SM, Gupta VA, Nooka AK, et al. Dexamethasone treatment promotes BCL2 dependence in multiple myeloma resulting in sensitivity to venetoclax. Leukemia. 2016;30(5):1086–1093. doi:10.1038/leu.2015.350
   PubMed Web of Science ®Google Scholar
• Gupta VA, Matulis SM, Barwick BG, et al. Venetoclax ex vivo functional profiling predicts improved progression-free survival. Blood Cancer J. 2022;12(8):115. doi:10.1038/s41408-022-00710-9
   PubMed Web of Science ®Google Scholar
• VENCLEXTA™ (Venetoclax) [prescribing information]. April 2021.
   Google Scholar
• Punnoose EA, Leverson JD, Peale F, et al. Expression profile of BCL-2, BCL-XL, and MCL-1 predicts pharmacological response to the BCL2 selective antagonist venetoclax in multiple myeloma models. Mol Cancer Ther. 2016;15(5):1132–1144. doi:10.1158/1535-7163.MCT-15-0730
   PubMed Web of Science ®Google Scholar
• FDA lifts partial clinical hold on phase 3 venetoclax study for patients with multiple myeloma; n.d. [cited 2023 Nov 19]. Available from: https://www.ajmc.com/view/fda-lifts-partial-clinical-hold-on-phase-3-venetoclax-study-for-patients-with-multiple-myeloma.
   Google Scholar
• Basali D, Chakraborty R, Rybicki L, et al. Real-world data on safety and efficacy of venetoclax-based regimens in relapsed/refractory t(11;14) multiple myeloma. Br J Haematol. 2020;189(6):1136–1140. doi:10.1111/bjh.16454
   PubMed Web of Science ®Google Scholar
• Szita VR, Mikala G, Kozma A, et al. Targeted venetoclax therapy in t(11;14) multiple myeloma: real world data from seven Hungarian centers. Pathol Oncol Res. 2022;28:1610276. doi:10.3389/pore.2022.1610276
   PubMed Web of Science ®Google Scholar
• Kaufman K, Gasparetto C, Schjesvold FH, et al. Phase I/II study evaluating the safety and efficacy of venetoclax in combination with dexamethasone as targeted therapy for patients with t(11;14) relapsed/refractory multiple myeloma. Blood. 2019;134(Supplement_1):926. doi:10.1182/blood-2019-125871
   Google Scholar
• Ong F, Kim K, Konopleva MY. Venetoclax resistance: mechanistic insights and future strategies. Cancer Drug Res. 2022;5(2):380–400. doi:10.20517/cdr.2021.125
   PubMedGoogle Scholar
• Fonseca R, Blood EA, Oken MM, et al. Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients. Blood. 2002;99(10):3735–3741. doi:10.1182/blood.V99.10.3735
   PubMed Web of Science ®Google Scholar
• Gupta VA, Barwick BG, Matulis SM, et al. Venetoclax sensitivity in multiple myeloma is associated with B-cell gene expression. Blood. 2021;137(26):3604–3615. doi:10.1182/blood.2020007899
   PubMed Web of Science ®Google Scholar
• Pentimalli F. BCL2: a 30-year tale of life, death and much more to come. Cell Death Differ. 2018;25(1):7–9. doi:10.1038/cdd.2017.189
   PubMed Web of Science ®Google Scholar
• He W, He F, Hu H. Efficacy and safety of venetoclax-based regimens in relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials. Ann Med. 2023;55(1):1029–1036. doi: 10.1080/07853890.2023.2186480
   PubMed Web of Science ®Google Scholar
• Chakraborty R, Bhutani D, Lentzsch S. How do we manage t(11;14) plasma cell disorders with venetoclax? Br J Haematol. 2022;199(1):31–39. doi:10.1111/bjh.18243
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network (NCCN) Guidelines. Multiple myeloma version 3; 2023 [cited 2023 May 11]. Available from: https://www.nccn.org.
   Google Scholar
• Ascentage Pharma received clearance from U.S. FDA to proceed with global registrational phase III clinical trial for lisaftoclax (APG-2575) in previously treated patients with CLL/SLL. News release. Ascentage Pharma; 2023. [cited 2023 Oct 8]. Available from: https://tinyurl.com/2fsu9ak7.
   Google Scholar
• Davids M, Chanan-Khan A, Mudenda B, et al. Lisaftoclax (APG-2575) safety and activity as monotherapy or combined with acalabrutinib or rituximab in patients (pts) with treatment-naïve, relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL): initial data from a phase 2 global study. Blood. 2022;140(1):2326–2328. doi:10.1182/blood-2022-160386
   Google Scholar
• Deng J, Paulus A, Fang DD, et al. Lisaftoclax (APG-2575) Is a novel BCL2 inhibitor with robust antitumor activity in preclinical models of hematologic malignancy. Clin Cancer Res. 2022;28(24):5455–5468. doi:10.1158/1078-0432.CCR-21-4037
   PubMed Web of Science ®Google Scholar