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Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Luciano J Costa1, Faith E Davies2, Gregory P Monohan3

  • 1Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL.

Blood Advances
|September 1, 2021
PubMed

Insights

The combination of venetoclax, carfilzomib, and dexamethasone (VenKd) shows promising results for relapsed/refractory multiple myeloma (RRMM). This treatment was well-tolerated and demonstrated high response rates, particularly in patients with t(11;14).

Area of Science:

  • Hematology
  • Oncology
  • Clinical Pharmacology

Background:

  • The B-cell lymphoma 2 (BCL-2) protein family is implicated in multiple myeloma (MM) pathophysiology.
  • Venetoclax, a BCL-2 inhibitor, induces apoptosis in MM cells and may enhance efficacy when combined with other agents.
  • Combination therapies are explored to improve outcomes in relapsed/refractory multiple myeloma (RRMM).

Purpose of the Study:

  • To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of venetoclax in combination with carfilzomib and dexamethasone (VenKd) in adults with RRMM.
  • To determine optimal dosing through a phase 2 dose-escalation study.

Main Methods:

  • A phase 2, dose-escalation study involving 4 dose-finding cohorts and an expansion cohort.
  • Patients received oral venetoclax (400 or 800 mg daily) combined with intravenous carfilzomib (27, 56, or 70 mg/m2) and oral dexamethasone (20 or 40 mg).
  • Forty-nine patients with RRMM were enrolled, with a median of 1 prior line of therapy.

Main Results:

  • The overall response rate (ORR) was 80% across all patients, with 92% in the t(11;14) subgroup and 75% in those without.
  • The rate of complete response or better was 41%, and the median progression-free survival was 22.8 months.
  • Common adverse events included diarrhea, fatigue, and nausea; 53% of patients experienced serious adverse events.

Conclusions:

  • The VenKd combination demonstrated good tolerability and promising antitumor activity in patients with RRMM.
  • Higher response rates were observed in patients with the t(11;14) genetic abnormality.
  • Further investigation of VenKd in RRMM is warranted.

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