Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14)
Details
Publication Year 2021-11,Volume 39,Issue #32,Page 3602-3612
Journal Title
Journal of Clinical Oncology
Publication Type
Research article
Abstract
PURPOSE: Venetoclax is an oral BCL-2 inhibitor with single-agent activity in patients with relapsed or refractory multiple myeloma (RRMM) with t(11;14) translocation. Venetoclax efficacy in RRMM may be potentiated through combination with agents including bortezomib, dexamethasone, and daratumumab. METHODS: This phase I study (NCT03314181) evaluated venetoclax with daratumumab and dexamethasone (VenDd) in patients with t(11;14) RRMM and VenDd with bortezomib (VenDVd) in cytogenetically unselected patients with RRMM. Primary objectives included expansion-phase dosing, safety, and overall response rate. Secondary objectives included further safety analysis, progression-free survival, duration of response, time to progression, and minimal residual disease negativity. RESULTS: Forty-eight patients were enrolled, 24 each in parts 1 (VenDd) and 2 (VenDVd). There was one dose-limiting toxicity in part 1 (grade 3 febrile neutropenia, 800 mg VenDd). Common adverse events with VenDd and VenDVd included diarrhea (63% and 54%) and nausea (50% and 50%); grade >/= 3 adverse events were observed in 88% in the VenDd group and 71% in the VenDVd group. One treatment-emergent death occurred in part 2 (sepsis) in the context of progressive disease, with no other infection-related deaths on study with medians of 20.9 and 20.4 months of follow-up in parts 1 and 2, respectively. The overall response rate was 96% with VenDd (all very good partial response or better [>/= VGPR]) and 92% with VenDVd (79% >/= VGPR). The 18-month progression-free survival rate was 90.5% (95% CI, 67.0 to 97.5) with VenDd and 66.7% (95% CI, 42.5 to 82.5) with VenDVd. CONCLUSION: VenDd and VenDVd produced a high rate of deep and durable responses in patients with RRMM. These results support continued evaluation of venetoclax with daratumumab regimens to treat RRMM, particularly in those with t(11;14).
Keywords
Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal/adverse effects/pharmacokinetics/*therapeutic use; Antineoplastic Combined Chemotherapy Protocols/adverse; effects/pharmacokinetics/*therapeutic use; Australia; Bortezomib/adverse effects/pharmacokinetics/*therapeutic use; Bridged Bicyclo Compounds, Heterocyclic/adverse; effects/pharmacokinetics/*therapeutic use; *Chromosomes, Human, Pair 11; *Chromosomes, Human, Pair 14; Dexamethasone/adverse effects/pharmacokinetics/*therapeutic use; Europe; Female; Humans; Male; Middle Aged; Multiple Myeloma/*drug therapy/genetics/mortality/pathology; Neoplasm, Residual; North America; Progression-Free Survival; Sulfonamides/adverse effects/pharmacokinetics/*therapeutic use; Time Factors; *Translocation, Genetic
Department(s)
Haematology
PubMed ID
34388020
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