Adding daratumumab to standard combination of lenalidomide and dexamethasone (Rd) reduced the risk of disease progression and death by 44 percent in patients with newly diagnosed multiple myeloma (MM) who were ineligible for transplantation, according to results from the phase III MAIA trial. This combination also was associated with a greater response rate and deeper responses, compared with Rd alone.
“The results from this study are enough to establish daratumumab plus Rd as a new standard of care for patients who are ineligible for transplant,” said Thierry Facon, MD, from the Hôpital Claude Huriez in Lille, France, during his presentation of the results at the 2018 ASH Annual Meeting.
The randomized, open-label trial enrolled 737 adults with previously untreated MM who were considered ineligible for high-dose chemotherapy with autologous stem cell transplantation – primarily due to age (≥65 years) or comorbidities.
Participants were stratified according to disease stage (per International Staging System [ISS] stage), region, and age <75 vs. ≥75 years), then randomized 1:1 to receive either:
- Rd: lenalidomide 25 mg daily on days 1-21 and dexamethasone 40 mg weekly in 28-day treatment cycles (n=369)
- Rd plus daratumumab: 16 mg/kg weekly (n=368)
Patient characteristics were well balanced between each arm, Dr. Facon said, noting that 44 percent of patients were older than 75 years, which is higher than in other trials of myeloma. Participants’ median age was 73 years (range = 45-90 years).
After a median follow-up of 28 months (range = 0-41.4 months), median progression-free survival (PFS; the primary endpoint) was not reached in the daratumumab-plus-Rd group and 31.9 months in the Rd group. The 30-month PFS was 71 percent and 56 percent, respectively, for a hazard ratio of 0.56 in favor of the daratumumab group (95% CI 0.43-0.73; p<0.001).
Results of analyses for secondary endpoints (overall response rate [ORR] and minimal residual disease [MRD]) also favored the daratumumab group. For daratumumab, ORR was 93 percent, compared with 81 percent in the Rd group (p<0.001), with a greater number of complete responses in the daratumumab group (48% vs. 25%; p<0.001). MRD-negativity rates (with a sensitivity of 10-5) were 24 percent and 7 percent, respectively (p<0.001).
While these are preliminary data, he said, the safety analysis showed that daratumumab plus Rd is “gentle” enough for older patients. “The [adverse events] were manageable, and the safety profile was consistent with findings from other studies of daratumumab plus standards of care,” Dr. Facon added.
Incidence of grade 3/4 neutropenia and pneumonia was higher in patients treated with the daratumumab combination (50% vs. 35% and 14% vs. 8%, respectively), while incidence of grade 3/4 anemia and thrombocytopenia were more common in the Rd group (20% vs. 12% and 9% vs. 7%). However, p values were not reported for these comparisons.
The incidence of infusion-related reactions in the daratumumab arm was “as expected,” he noted, at 41 percent, and “very few, 3 percent, were grade 3 or 4.” Three percent and 4 percent of patients in the daratumumab and Rd groups, respectively, developed a secondary primary malignancy, and the incidence of treatment-emergent adverse events leading to death was 7 percent and 6 percent, respectively.
Dr. Facon noted that the overall survival data from the MAIA trial are not yet mature, which limits comparisons between the daratumumab combination and other regimens for the treatment of myeloma. For example, bortezomib plus Rd has become a standard of care in several countries, with a PFS of approximately 36 months.
Dr. Facon also acknowledged that other combinations and maintenance regimens are associated with more toxicity, making them unsuitable for older, frail patients – like the population enrolled in MAIA. Regardless, he said, “it is good for patients to have more than one option.”
The authors report financial relationships with KITE, AbbVie, and Janssen, the sponsor of the trial.
Facon T, Kumar SK, Plesner 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). Abstract #LBA-2. Presented at the 2018 ASH Annual Meeting, December 4, 2018; San Diego, CA.