Daratumumab maintenance therapy after autologous stem-cell transplant in patients with newly diagnosed multiple myeloma.

This study investigated the use of daratumumab (Darzalex) as maintenance therapy following autologous stem-cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM). The data showed that maintenance therapy with daratumumab resulted in significant improvements in outcomes compared to observation only in patients that received ASCT.

Patients with multiple myeloma (a cancer of blood cells called plasma cells) can have tumor growth even after treatment (relapse). The Standard of care for patients with NDMM consists of induction therapy (first-line therapy), stem cell replacement with patients’ healthy stem cells (ASCT), and consolidation therapy (treatment to kill residual cancer cells).

Approved treatments for patients with NDMM that are eligible for ASCT include D-VTd (daratumumab, bortezomib, thalidomide, and dexamethasone). Long-term maintenance therapy can be done to enhance frontline therapy responses and to prevent cancer return. Although lenalidomide (Revlimid) improves progression-free survival (PFS) and overall survival (OS), it is not well-tolerated by some patients. There is a need to explore alternatives to lenalidomide for possible maintenance therapy.

This study included 886 patients with NDMM. Patients were initially treated with D-VTd or VTd and ASCT. These patients were randomly assigned to 2 groups. Group 1 included 442 patients who received daratumumab maintenance every 8 weeks. Group 2 included 444 patients who underwent observation only. Patients were followed for up for an average of 35.4 months.

The average survival without cancer worsening was not reached when this analysis was done (still ongoing) for group 1 compared to 46.7 months for group 2. Patients in group 1 were 47% more likely to have a longer survival without cancer worsening. 

The rate of complete response (no signs of cancer) was higher in group 1 (73%) compared to group 2 (61%). Also, significantly more patients in group 1 had negative minimal residual disease (MRD; a small number of cancer cells left after treatment that are the reason for cancer relapse) compared to group 2 (59% vs. 47%)

Overall, 95% of patients in group 1 had side effects compared to 89% in group 2. 23% of the patients in group 1 had serious side effects compared to 19% in group 2. These included pneumonia and lung infection.

The study showed that daratumumab maintenance every 8 weeks reduced the risk of disease progression or death compared to observation only in patients with NDMM treated with ASCT.

This study included different trial designs and the duration of maintenance was only up to 2 years. Additional head-to-head comparisons using lenalidomide and longer follow-ups are needed. This study was funded by Janssen, the manufacturer of daratumumab.