Venetoclax is the first drug that was determined to work for a specific type of genetic feature found in multiple myeloma patients called the 11;14 translocation. This means that part of chromosome 11 has swapped places with parts of chromosome 14 on the myeloma cells. This is the most common translocation found in myeloma patients (20% of patients) and is found to be a standard risk feature. Venetoclax works as a BCL-2 inhibitor and other relapsed or refractory myeloma patients can respond to it as well.
In a Phase 1/2 study (ECOG-ACRIN EAA172), researchers compared daratumumab/bortezomib/dex with daratumumab/bortezomb/dex/venetoclax. In these early studies, safety and dosing are always the goal. This study went on clinical hold (meaning it could not recruit new patients) because of data that came out in a separate study using venetoclax with bortezomib and dex (the BELLINI trial).
Combination therapy with daratumumab and bortezomib (DVd) has become a standard of care in relapsed/refractory myeloma and the hypothesis is that adding venetoclax could improve outcomes, especially for the t(11;14) patients.
In the Phase II study, 240 patients will be included with 1/3 of patients having t(11;14) and 2/3 of patients having no t(11;14). Investigators are looking forward to the continuation and results of this study.