In a phase I study reported in the Journal of Clinical Oncology, Bahlis et al found that venetoclax plus daratumumab/dexamethasone (VenDd) and VenDd with bortezomib (VenDVd) produced high rates of durable responses in patients with relapsed or refractory multiple myeloma with t(11;14) translocation and among cytogenetically unselected patients with relapsed or refractory multiple myeloma, respectively.
Study Details
Patients from sites in the United States, Australia, Canada, Denmark, and France were enrolled into the trial between April 2018 and March 2019, including 24 patients with t(11;14) treated with VenDd in part 1 and 24 cytogenetically unselected patients treated with VenDVd in part 2. Among patients in the dose-escalation cohorts, 5 of 11 in part 1 and 4 of 9 in part 2 received venetoclax at 400 mg once daily. The expansion-phase dose of venetoclax in both parts was 800 mg once daily. VenDd was given in 28-day cycles; VenDVd was given in 21-day cycles in cycles 1 to 8 and 28-day cycles thereafter.
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.
Key Findings
Median follow-up was approximately 21 months (range = 19–30 months) among patients treated with VenDd and approximately 21.5 months (range = 19–26 months) among those treated with VenDVd.
Response (all very good partial response or better) was observed in 23 patients (96%) receiving VenDd, with complete response in 58%, and in 22 (92%) of those receiving VenDVd (very good partial response or better in 79%), with compete response in 46%. Response was observed in five of six patients with t(11;14) receiving VenDVd. Median duration of response was not reached in either group, with response persisting for ≥ 18 months in 90.5% and 70% of responders, respectively. Measurable residual disease–negative (< 10-5) response was achieved in 33% and 21% of responders.
Median progression-free survival was not reached in either group. Estimated progression-free survival rates at 18 months were 90.5% with VenDd and 66.7% with VenDVd.
Common adverse events of any grade seen with VenDd and VenDVd included diarrhea (63% and 54%) and nausea (50% and 50%). Grade ≥ 3 adverse events were observed in 88% and 71% of patients; the most common were hypertension (17%) with VenDd and insomnia (25%) with VenDVd. Grade ≥ 3 infections occurred in 25% and 21% of patients. Serious adverse events occurred in 54% and 33%. There were no treatment-related deaths.
The investigators concluded, “VenDd and VenDVd produced a high rate of deep and durable responses in patients with relapsed or refractory multiple myeloma. These results support continued evaluation of venetoclax with daratumumab regimens to treat relapsed or refractory multiple myeloma, particularly in those with t(11;14).”
Nizar J. Bahlis, MD, of the Arnie Charbonneau Cancer Institute, University of Calgary, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was sponsored by AbbVie. For full disclosures of the study authors, visit ascopubs.org.
