Oral presentation by Dr. Thierry Facon
The MAIA study compared the daratumumab and lenalidomide plus dexamethasone (DRd) regimen to the lenalidomide plus dexamethasone (Rd) regimen in patients with newly diagnosed multiple myeloma (NDMM) and interim results are presented at ASH 2018. NDMM patients who are ineligible for a transplant were randomized 1:1 between DRd (n = 368) and Rd (n = 369). Rd was given until progression, identically in both arms. Daratumumab was administered once a week (cycle 1 and 2), then once every 2 weeks (cycles 3–6), and then once every 4 weeks from cycle 7 until progression. The primary objective was progression-free survival (PFS), while secondary objectives included complete response (CR) rate, very good partial response, minimal residual disease (MRD) negativity, overall response rate (ORR), overall survival (OS), and tolerance.
In the overall population, 44% of patients were over the age of 75 (median age 73 years old), 29% had an International Staging System score of 3, and 14% were at high cytogenetic risk. At the time of reporting, 32% of the DRd arm and 57% of the Rd arm had discontinued the study mainly due to progression (15% and 24%, respectively) or to side effects (7% and 16%, respectively).
In terms of efficacy, with a median follow-up of 28 months, the median PFS of the DRd arm was not reached and that of Rd was 31.9 months. The 30-month PFS was 71% versus 56% in favour of the DRd arm. All subgroups appear to benefit from the DRd regimen, with the exception of the high-cytogenetic-risk group.
In terms of response rate, the ORR was 93% versus 81% (p <0.0001) in favour of DRd, whose CR rate was 48% compared to 25% for Rd. The MRD negativity rate was 3.4 times higher in the DRd arm than in the Rd arm (24% vs. 7%, p <0.0001). The OS data were not yet mature but there was already a trend in favour of DRd, albeit with few events. Tolerance was consistent with the toxicity profile of the molecules with predominantly hematological toxicity (50% had grade 3/4 neutropenia in the DRd arm versus 35% for Rd).
The preliminary favourable results of this study could in the future establish the DRd regimen as a first-line standard. A more prolonged follow-up is nevertheless necessary to reach a conclusion. The analysis of the PFS curves suggests better results than those of the SWOG S0777 study, which showed a median PFS of 43 months for bortezomib and lenalidomide plus dexamethasone versus 30 months for Rd. The results for the median PFS of the Rd arm are very comparable between MAIA and SWOG S0777 (31.9 and 30 months). Finally, the relative simplicity and good tolerance of the DRd regimen work in its favour compared to the daratumumab, bortezomib, melphalan, and prednisone regimen in the ALCYONE study.