King Edward Medical University, Lahore, Pakistan
Zahoor Ahmed , Shaha Nabeel , Arafat Ali Farooqui , Hassan Imtiaz , Aqsa Ashraf , Umer Farooq , Mohammad Ammad Ud Din , Ahsan Wahab , Saif ur Rehman , Faiz Anwer
Background: In multiple myeloma (MM), translocation t(11;14) has shown higher expression of B Cell Lymphoma 2 protein (BCL2)- a target for Venetoclax (VEN). This review highlights the role of precision therapy with VEN in t(11;14) MM. Methods: A systematic search of PubMed, Cochrane, Web of Science and Clinicaltrials.gov was performed for use of VEN in MM from inception to 1/2/20. 5 out of 183 studies were finalized (N = 512). Results: Out of 500 relapsed refractory (R/R) MM patients, 97 had t(11;14) and 168 had high BCL2. VEN as monotherapy had encouraging responses in t(11;14) MM patients with high BCL2:BCL2L1 (Kumar 2017). VEN when combined with proteasome inhibitors (PIs) achieved promising results. VEN achieved superior results with carfilzomib and dexamethasone (d) (ORR 100%) in t(11;14) MM patients (Costa 2018) as compared to bortezomib (B) and d (ORR 94%) (Moreau 2017). With high BCL2, VEN-Bd achieved ORR of 84% (CR 35%, VGPR 73%) versus placebo (ORR 83%; VGPR 33%) (Bellini 2019). Conclusions: Venetoclax achieved superior responses in RRMM pts with t(11;14) and high BCL2 expression. Further studies are warranted.
Trial ID (NCT) | Author, Year; Phase | Regimen | N(n) | Median age (years) | Median number of prior therapies | Efficacy* | Toxicities (Grade≥3) |
---|---|---|---|---|---|---|---|
Retrospective | Kambhampati. 2020 | VEN-PI | 47 | N/A | 07 | ORR: 71% ≥VGPR:24% | N/A |
02755597 | Bellini 2019 (II) | VEN-Bd vs Pbo-Bd | 291 | 66 | 1-3 | ORR: 95% vs 47% CR: 55% vs 7% VGPR: 75% vs 27% | N/A |
01794520 | Kumar 2017 (I) | VEN | 66 | 63 | 05 | ORR: 40% CR: 10% sCR: 04% PR: 13% VGPR:13% | Anemia (14%), neutropenia (21%), thrombocytopenia (26%), leukopenia (14%), lymphopenia (15%) |
01794507 | Moreau 2017 (Ib) | VEN-Bd | 66 | 64 | 03 | CR: 11% PR: 78% | Thrombocytopenia (29%), anemia (15%), neutropenia (14%) |
02899052 | Costa 2018 (II) | VEN-Cd | 42(30) | 67 | 02 | ORR:100% CR: 29% sCR: 14% PR: 14% VGPR:43% | Leukopenia (10%), lymphopenia (10%) |
*Table reports efficacy of t(11;14) mutation sub-population
Abbreviations: VEN: Venetoclax, B: Bortezomib, C: Carfilzomib, d: dexamethasone, PI: Proteasome Inhibitor, N: Number of patients enrolled, n: Evaluable patients, ORR: Overall response rate, sCR: Stringent Complete response, CR: Complete response, PR: Partial response, VGPR: Very good partial response, ≥VGPR: Very good partial response or better, NA: not available, mo: months, Pbo: Placebo, pt: patient.
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Abstract Disclosures
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