Durable MRD negativity was associated with improved progression-free survival (PFS) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) in long-term follow-up of two large randomized clinical trials. While the association of durable MRD negativity with improved PFS held regardless of treatment regimen, more patients who received daratumumab-based therapies achieved MRD negativity and maintained it for at least 6 or 12 months. The findings were reported in Blood on January 27, 2022.
The Phase III MAIA and ALCYONE trials enrolled more than 737 and 706 patients, respectively, with NDMM who were ineligible for high-dose chemotherapy or stem cell transplantation due to age (65 or older) or coexisting conditions. Patients were randomized to either lenalidomide plus dexamethasone (MAIA) or bortezomib plus melphalan plus prednisone (ALCYONE) plus or minus daratumumab. Previously reported results showed that the addition of daratumumab reduced the risk of disease progression or death by 44% in MAIA and by 58% in ALCYONE.
In a secondary analysis with a median follow-up of 36.4 months for patients enrolled in MAIA and 40.1 months for those enrolled in ALCYONE, treatment with daratumumab was associated with both improved PFS and with significantly higher rates of both MRD negativity and MRD negativity that was sustained for at least 6 or 12 months.
These data suggest that “durable MRD negativity lasting ≥6 or ≥12 months may represent yet a deeper level of response with a higher prognostic value, suggesting MRD negativity may be a more robust evaluation of disease control if sustained over time,” conclude first author Jesus San-Miguel, of the Clinica Universidad de Navarra in Spain, and coauthors.
- San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022;139(4):492-501. doi:10.1182/blood.2020010439
- Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249
- Mateos MV, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020;395(10218):132-141. doi:10.1016/S0140-6736(19)32956-3
Tags: MRD, transplantation, Cellular therapy, negativity, Transplant, cell therapy, PFS, NDMM, durable, associated, improved