Daratumumab-based regimens are associated with prolonged minimal residual disease (MRD) negativity in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), according to results from the MAIA and ALCYONE trials published in Blood.1
Previous results from the phase 3 MAIA trial (ClinicalTrials.gov Identifier: NCT02252172) showed that adding daratumumab to lenalidomide and dexamethasone (dara-Rd) reduced the risk of disease progression or death by 44%.2
In the phase 3 ALCYONE trial (ClinicalTrials.gov Identifier: NCT02195479), adding daratumumab to bortezomib, melphalan, and prednisone (dara-VMP) reduced the risk of disease progression or death by 58%.3
In the current analysis, researchers evaluated MRD status and the durability of MRD negativity in both MAIA and ALCYONE.
In the MAIA trial, the intent-to-treat (ITT) population included 737 NDMM patients who were randomly assigned to receive dara-Rd (368 patients) or Rd (369 patients). The median follow-up was 36.4 months.
The ITT population of the ALCYONE trial included 706 NDMM patients who were randomly assigned to receive dara-VMP (350 patients) or VMP (356 patients). The median follow-up was 40.1 months.
Daratumumab was associated with significantly higher rates of MRD negativity in the ITT population and among patients who achieved a complete response (CR) or better. Rates of MRD negativity were:
- 28.8% with dara-Rd vs 9.2% with Rd in the ITT population (P <.0001)
- 26.9% with dara-VMP vs 7.0% with VMP in the ITT population (P <.0001)
- 58.2% with dara-Rd vs 34.0% with Rd in the CR or better group (P =.0001)
- 58.8% with dara-VMP vs 27.8% with VMP in the CR or better group (P <.0001).
Daratumumab was associated with significantly higher rates of prolonged MRD negativity as well. Rates of MRD negativity lasting 12 months or more were:
- 10.9% in the dara-Rd arm vs 2.4% in the Rd arm in the ITT population (P <.0001)
- 14.0% in the dara-VMP arm vs 2.8% in the VMP arm in the ITT population (P <.0001)
- 22.0% in the dara-Rd arm vs 9.0% in the Rd arm in the CR or better group (P =.0053)
- 30.6% in the dara-VMP arm vs 11.1% in the VMP arm in the CR or better group (P =.0006).
The higher rates of MRD negativity with daratumumab led to prolonged progression-free survival (PFS), according to the researchers. A pooled analysis showed improved PFS in patients who were MRD negative for at least 6 months or at least 12 months, compared with patients who did not have sustained MRD negativity.
“Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes,” the researchers concluded.
Disclosures: Both MAIA and ALCYONE were supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. San-Miguel JF, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity with daratumumab in newly diagnosed multiple myeloma: MAIA and ALCYONE. Blood. Published online July 16, 2021. doi:10.1182/blood.2020010439
2. Facon T, Kumar S, Plesner T, el al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249
3. 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