Effects of combined treatment with venetoclax, daratumumab and dexamethasone with or without bortezomib in patients with relapsed or refractory multiple myeloma.

This study evaluated the effectiveness and safety of a venetoclax (Venclexta), daratumumab (Darzalex), and dexamethasone (Decadron combination with or without bortezomib (Velcade) in patients with relapsed or refractory (RR) multiple myeloma (MM). The authors concluded that these treatment combinations produced high and long-term responses in these patients. 

MM is a cancer of a type of white blood cell called a plasma cell. Although newer therapies are available for MM, many patients experience relapse (reappearance of MM after initial improvement) or they become refractory (no improvement with treatment). To maximize treatment effects for patients with RRMM, combination therapies are often used but an optimal choice of therapy has not been determined.

Venetoclax (Ven) is a targeted therapy that blocks a protein called BCL-2 that helps cancer cells live and spread. Daratumumab and dexamethasone (Dd) is a combination commonly used in the treatment of MM. Another therapy commonly used is bortezomib (V). V is a proteasome inhibitor that works by blocking proteasomes, which break down proteins in the cell. By blocking proteasomes, V stops MM cells divide.

Small studies have shown that adding Ven to Vd treatment improves the outcomes of patients with RRMM. However, there is a need to further assess this treatment combination for developing an optimal choice of therapy for RRMM.

This study included 48 patients with RRMM. There were 2 parts in this study. Part 1 included 24 patients with a genetic mutation (change) called t(11;14). These patients received Ven-Dd. Part 2 included 24 patients that were not selected based on genetic mutations. They received Ven-DVd. The average study follow-up was 21 months for Part 1 and 21.5 months for Part 2.

Overall, 96% of patients in Part 1 and 92% in Part 2 responded to treatment. 58% of patients in Part 1 and 46% in Part 2 had a complete response (no signs of cancer). 

Minimal residual disease (MRD) is an outcome that evaluated the number of cancer cells left after treatment. MRD negativity means that there are no cancer cells left. 33% of the patients in Part 1 and 21% in Part 2 were MRD-negative. 90.5% of patients in Part 1 and 70% in Part 2 were still responding to treatment after 18 months. 

The most common side effects were diarrhea, tiredness, nausea, high blood pressure, and insomnia. 88% of patients in Part 1 and 71% in Part 2 experienced severe side effects. 

The study showed that VenDd and VenDVd produced high, and long-standing responses in patients with RRMM.

This study had a very small number of participants and a short follow-up period. Larger studies are needed to confirm these results. This study was funded by AbbVie, the manufacturer of venetoclax.