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

Luciano J. Costa, Faith E. Davies, Gregory P. Monohan, Tibor Kovacsovics, Nicholas Burwick, Andrzej Jakubowiak, Jonathan L. Kaufman, Wan Jen Hong, Monique Dail, Ahmed Hamed Salem, Xiaoqing Yang, Abdullah A. Masud, Wijith Munasinghe, Jeremy A. Ross, Orlando F. Bueno, Shaji K. Kumar, Edward A. Stadtmauer

Research output: Contribution to journalArticlepeer-review


Proteins in the antiapoptotic B-cell lymphoma 2 (BCL-2) family play a role in the pathophysiology of multiple myeloma (MM). Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis of MM cells, and its efficacy may be potentiated through combination with agents that increase BCL-2 dependency or have complementary mechanisms of action. The safety, tolerability, pharmacokinetics, and antitumor activity of venetoclax in combination with carfilzomib and dexamethasone (VenKd) in adults with relapsed/refractory MM (RRMM) were investigated in this phase 2 dose-escalation study. Oral venetoclax (400 or 800 mg) was administered daily in combination with intravenous carfilzomib (27, 56, or 70 mg/m2) and oral dexamethasone (20 or 40 mg) in 4 dose-finding cohorts. The expansion cohort received venetoclax 800 mg, carfilzomib 70 mg/m2, and dexamethasone 40 mg. Forty-nine patients received treatment. Median prior lines of therapy was 1 (range, 1-3), and median time in the study was 27 months. The most common treatment-emergent adverse events were diarrhea (65%), fatigue (47%), nausea (47%), and lymphopenia (35%). Serious adverse events occurred in 26 (53%) patients. Of 3 treatment-emergent deaths, 1 was considered treatment related. The overall response rate was 80% in all patients, 92% in patients with t(11;14) (n 5 13), and 75% in patients without (n 5 36). The rate of complete response or better was 41%. Median progression-free survival was 22.8 months. Treatment with VenKd was well tolerated and showed promising response rates in this RRMM patient population, with greater responses observed in patients with t(11;14). This trial is registered at as #NCT02899052.

Original languageEnglish (US)
Pages (from-to)3748-3759
Number of pages12
JournalBlood Advances
Issue number19
StatePublished - Oct 12 2021

ASJC Scopus subject areas

  • Hematology


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