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 (RRMM) who have a t(11;14) abnormality.
There are 3 parts to the study. Part 1 included 24 patients with t(11;14) ranging in age from 51 to 76 years who had previously undergone ≥1 prior treatment regimens consisting 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).
In part 1, the overall response rate (ORR) was 95.8%, and all patients had a very good partial response rate or better. 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 regardless of t(11;14) status ranging in age from 41 to 80 years were enrolled; 6 of these patients had t(11;14) translocation. 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). In part 2, the ORR was 91.7%; 79.1% had a very good partial response rate or better. Median follow-up time was 9 months, and median PFS and DOR rates were not reached.
Of the 48 patients who were enrolled, the most frequent adverse events (AEs) in parts 1 and 2 of the study that occurred were fatigue in 71% and 25%, diarrhea in 63% and 71%, and nausea in 50% and 50%, respectively, as of December 2019. In study patients in parts 1 and 2, insomnia (33%, 54%), upper respiratory tract infection (38%, 21%), cough (38%, 13%), and arthralgia (25%, 21%) also frequently occurred. For patients in part 1, grade ≥3 AEs included neutropenia (17%), hypertension (12%), fatigue (8%), and hyperglycemia (8%), and for patients in part 2, the most common grade ≥3 AEs were insomnia (21%), diarrhea (8%), and thrombocytopenia (8%). Eighteen patients, 11 in group 1 and 7 in group 2, had serious AEs, with the most common being pyrexia observed in 3 patients. In parts 1 and 2, infection-related grade ≥3 AEs occurred in 5 and 4 patients, respectively. The pharmacokinetic data showed that the antitumor activity of venetoclax was not impacted by the combination of daratumumab and bortezomib. 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).
In part 3 of the study, a randomized, open-label extension that will examine VenDd (400 or 800 mg Ven) with patients with t(11;14) on DVd will be included.
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.