Interim results from a large international phase III clinical trial show that adding daratumumab to standard therapy significantly progression-free survival (PFS) in patients newly diagnosed with multiple myeloma who were ineligible for a stem cell transplant.
A stem cell transplant is often a recommended treatment option for patients with multiple myeloma who are otherwise in good health. For newly diagnosed patients who aren’t candidates for a stem cell transplant due to age or coexisting health conditions, lenalidomide and dexamethasone (Rd) has been the standard of care since 2013.
The current trial, known as the MAIA study, enrolled 737 patients with newly diagnosed multiple myeloma who were deemed ineligible for a stem cell transplant. Their median age was 73, with 44% over 75. Slightly over half of the patients were male. The trial was conducted in 14 countries, including the United States, Canada, Australia, Israel, the United Kingdom, and several European countries.
Patients were randomly assigned to be treated with either Rd alone or Rd plus daratumumab (DARA). Treatment continued until the patients’ cancer got worse or intolerable side effects occurred. The primary endpoint was progression-free survival. Key secondary endpoints included minimal residual disease (MRD) negativity, the overall response rate (ORR) and the rate and severity of adverse side effects.
An interim analysis of the trial’s results after a median follow-up period of 28 months showed that patients treated with Rd plus DARA were 44% less likely to have died or experience disease progression, compared with patients who received Rd alone. Median PFS was 31,9 months for patients treated with Rd alone, and has not been reached yet for those who received Rd plus DARA.
The complete response rate was 47,6% for patients treated with Rd plus DARA, compared with 24,9% for those who received Rd alone. The proportion of patients who achieved a very good partial response or better also was significantly better among patients treated with Rd plus DARA (79,3% compared with 53,1% for patients treated with Rd alone). There was more than 3-fold improvement in achieving MRD negativity for Rd plus DARA (24,2 vs 7,3%) which translates into more patients having longer PFS than standard of care alone. In addition, Rd plus DARA helped more patients achieve a durable MRD response. While the safety profile in MAIA was in line with previous studies, more patients in the Rd-plus-DARA arm than in the Rd-alone arm experienced moderate or severe adverse effects of pneumonia and low white blood cell counts.
„These results support the addition of daratumumab to Rd as the new standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma,‟ said lead author Thierry Facon, MD, of Claude Huriez Hospital in Lille, France.
Facon T et al.: Phase 3 randomized study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) ineligible for transplant (MAIA). ASH Annual Meeting 2018, abstract #LBA3