Advances in precision therapy with venetoclax in multiple myeloma with t(11;14) and high BCL2 expression: A systematic review.

Authors

null

Zahoor Ahmed

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

Organizations

King Edward Medical University, Lahore, Pakistan, Zucker School of Medicine/Northwell Health at Mather, Port Jefferson, NY, Loyola Medicine/MacNeal Hospital, Berwyn, IL, Rochester General Hospital, Rochester, NY, Baptist Medical Center South/University of Alabama Birmingham, Montgomery, AL, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH

Research Funding

No funding received
None

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.

Efficacy and tolerability of venetoclax in RRMM with t(11;14).

Trial ID
(NCT)
Author, Year; PhaseRegimenN(n)Median age (years)Median
number of prior therapies
Efficacy*Toxicities
(Grade≥3)
RetrospectiveKambhampati. 2020VEN-PI47N/A07ORR: 71%
≥VGPR:24%
N/A
02755597Bellini 2019 (II)VEN-Bd vs Pbo-Bd291661-3ORR: 95% vs
47%
CR: 55% vs 7%
VGPR: 75% vs
27%
N/A
01794520Kumar 2017 (I)VEN666305ORR: 40%
CR: 10%
sCR: 04%
PR: 13%
VGPR:13%
Anemia (14%),
neutropenia
(21%),
thrombocytopenia
(26%),
leukopenia
(14%), lymphopenia
(15%)
01794507Moreau 2017 (Ib)VEN-Bd666403CR: 11%
PR: 78%
Thrombocytopenia
(29%), anemia (15%), neutropenia (14%)
02899052Costa 2018 (II)VEN-Cd42(30)6702ORR: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 Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Publication Only

Session Title

Publication Only: Hematologic Malignancies—Plasma Cell Dyscrasia

Track

Hematologic Malignancies

Sub Track

Multiple Myeloma

Citation

J Clin Oncol 38: 2020 (suppl; abstr e20535)

DOI

10.1200/JCO.2020.38.15_suppl.e20535

Abstract #

e20535

Abstract Disclosures