Long-term outcomes of daratumumab, bortezomib, and dexamethasone in previously treated patients with multiple myeloma.

This trial was carried out to examine the long-term safety and effectiveness of daratumumab (Darzalex) plus bortezomib (Velcade) and dexamethasone (Dexasone) in patients with previously treated multiple myeloma (MM). The authors concluded that after 3-years this treatment maintained benefit and was safe in these patients.

MM is a form of cancer that comes from white blood cells called plasma cells. Despite existing treatment options, MM is incurable. New targeted treatments have improved the outcomes of these patients.

Daratumumab binds to CD-38 (a protein found in high levels on MM cells) and activates the immune system to attack and kill MM cells. Bortezomib is an anti-cancer medication used in the treatment of MM. It blocks proteins found in MM cells called proteasomes. This leads to cancer cell death. Dexamethasone is a steroid drug that decreases inflammation which often is uncontrolled in cancer. The combination of daratumumab, bortezomib and dexamethasone (D-Vd) has shown to improve survival without disease worsening in a short-term study. However, the long term outcomes for this treatment combination in previously treated patients with MM remain under investigation. 

There were 498 patients with MM in this trial. Patients had previously received an average of 2 treatments. 251 patients received D-Vd treatment while 247 patients received bortezomib and dexamethasone (Vd) alone. The average follow-up was 40 months.

Overall, the average time patients were alive without disease worsening was significantly longer in the D-Vd group (16.7 months) compared to the Vd group (7.1 months). At 42 months, 22% of the D-Vd group and 1% of the Vd group were alive without disease worsening. 

The response rate was significantly higher in the D-Vd group when compared to the Vd group (85% vs. 63%). Minimal residual disease (MRD) is the small amount of cancer cells that may remain after treatment. MRD negativity means there are no cancer cells left. Significantly more patients in the D-Vd group were MRD negative at follow-up (14%) compared to the Vd group (2%). 

The most common severe side effects reported were a low platelet (blood cell involved in clotting) count (46% with D-Vd and 33% with Vd) and anemia (low red blood cell count; 16% in both groups). Other side effects were tingling in the feet (50% with D-Vd and 38% with Vd), upper respiratory infections (35% with D-Vd and 18% with Vd) or diarrhea (35% with D-Vd and 22% with Vd).

The authors found that after 3 years, D-Vd was safe and maintained significant benefits in patients with relapsed or refractory MM.

This study was sponsored by Janssen Research & Development LLC, the manufacturers of daratumumab.