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Venetoclax plus Daratumumab and Dexamethasone ± Bortezomib in Relapsed/Refractory Multiple Myeloma

Conference Correspondent

An ongoing phase 1/2, nonrandomized, multicenter study is exploring the safety profile, efficacy, and pharmacokinetics of adding daratumumab to venetoclax and dexamethasone with or without bortezomib for patients with relapsed/refractory multiple myeloma who have a t(11;14) abnormality. Part 1 of the study included 24 patients with t(11;14) ranging in age from 51 to 76 years who had previously undergone at least 1 prior treatment regimen that consisted of a proteasome inhibitor and an immunomodulatory drug. These patients were administered venetoclax daily plus daratumumab 16 mg/kg intravenously plus dexamethasone 40 mg weekly (VenDd).

The overall response rate (ORR) in part 1 was 95.8%, and all had a very good partial response rate or better. The median follow-up time was 10 months. Median progression-free survival (PFS) and duration of response (DOR) were not reached. In part 2 of the study, 24 patients ranging in age from 41 to 80 years regardless of t(11;14) status were enrolled; 6 of these patients had t(11;14) translocation. All of these patients had received 1 to 3 prior therapy regimens and were treated with venetoclax daily plus daratumumab 16 mg/kg intravenously, bortezomib 1.3 mg/m2, and dexamethasone 20 mg (VenDVd). The ORR in part 2 was 91.7%, and 79.1% had a very good partial response rate or better. The median follow-up time was 9 months, and median PFS and DOR were not reached.

As of December 2019, of the 48 enrolled patients, the most frequent adverse events (AEs) in part 1 and part 2 of the study were fatigue that occurred in 71% and 25%, diarrhea that occurred in 63% and 71%, and nausea that occurred in 50% and 50%, respectively. Insomnia (33%; 54%), upper respiratory tract infection (38%; 21%), cough (38%; 13%), and arthralgia (25%; 21%) also frequently occurred in part 1 and part 2 study patients. Grade ≥3 AEs for patients in part 1 included neutropenia (17%), hypertension (12%), fatigue (8%), and hyperglycemia (8%); for patients in part 2, the most common grade ≥3 AEs were insomnia (21%), diarrhea (8%), and thrombocytopenia (8%). Eighteen patients had a serious AE, 11 in group 1 and 7 in group 2, with the most common being pyrexia that was observed in 3 patients. Infection-related grade ≥3 AEs occurred in 5 patients in part 1, and 4 patients in part 2. The pharmacokinetics data showed that combining daratumumab and bortezomib did not impact the antitumor activity of venetoclax. In summary, the initial analysis of this ongoing study supports the safety and efficacy of venetoclax in combination with daratumumab and dexamethasone with or without bortezomib, notably among patients with t(11;14).

Part 3 of the study will include a randomized, open-label extension that will examine VenDd (400 mg or 800 mg Ven) with patients with t(11;14) on DVd.


Reference

  • Abstract and Poster EP940. EHA 2020. June 12, 2020. Updated results from a phase 1/2 study of venetoclax in combination with daratumumab and dexamethasone, +/- bortezomib, in patients with relapsed/refractory multiple myeloma.

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