Patients with multiple myeloma (MM) often relapse and develop refractory disease, challenging their oncology team to find the best treatment to control their disease. One drug often used is venetoclax, an oral BCL-2-inhibitor known to show activity against MM with a t(11;14) translocation. They also must consider what agents would improve the effectiveness of venetoclax in these patients. 

Treatment regimens that combine venetoclax with daratumumab look promising, especially for patients with relapsed or refractory multiple myeloma (RRMM) with a t(11;14) translocation, according to the results of a Phase 1 study recently published in the Journal of Clinical Oncology

A total of 48 patients were enrolled in a phase 1 study with the goal of evaluating a regimen of venetoclax with daratumumab and dexamethasone (VenDd) in patients with t(11;14) RRMM and a regimen of VenDd with bortezomib (VenDVd) in cytogenetically unselected patients with RRMM. 

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Overall response rates were 96% in VenDd group and 92% in VenDVd group. The researchers also found 18-month progression-free survival rate was 90.5% in patients receiving VenDd and 66.7% in patients receiving VenDVd. 

“In this study, treatment with VenDd and VenDVd resulted in notable efficacy and acceptable safety in patients with t(11;14) RRMM and cytogenetically unselected RRMM, respectively,” the researchers wrote. “Although differences in the study population and treatment schedule between the VenDd and VenDVd arms prevent direct comparison between the two arms, neither combination had new safety signals, and the addition of daratumumab to 800 mg oral venetoclax daily did not appear to alter the known safety profiles of venetoclax or daratumumab combinations.” 

The researchers noted that this study did contain a small number of patients with t(11;14) and differences in the daratumumab and dexamethasone treatment schedule in the VenDVd arm. But the patients responded in similar ways to both VenDd and VenDVd, and “response rates in patients with t(11;14) RRMM appeared to be improved over those previously reported in similar populations treated with venetoclax monotherapy or combinations.” 

A phase 2 study will build upon this research, enrolling patients with t(11;14) RRMM into a randomized, open-label expansion cohort to evaluate VenDd with a DVd control arm to contextualize safety results, the researchers reported. 

Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Bahlis NJ, Baz R, Harrison SJ, et al. Phase I study of venetoclax plus daratumumab and dexamethasone, with or without bortezomib, in patients with relapsed or refractory multiple myeloma with and without t(11;14).  Journal of Clinical Oncology. Published online August 13, 2021. doi:10.1200/JCO.21.00443