Adding daratumumab to lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) in transplant-ineligible patients with newly diagnosed multiple myeloma (MM), regardless of frailty status, according to a subgroup analysis of the MAIA study published in Leukemia.1
The phase 3 MAIA trial (ClinicalTrials.gov Identifier: NCT02252172) included 737 patients — 368 who were randomly assigned to receive D-Rd and 369 assigned to lenalidomide and dexamethasone (Rd). Prior results showed that D-Rd improved PFS over Rd.2
For the current analysis, researchers compared the 2 regimens across frailty subgroups. Patients were divided into 3 subgroups — fit, intermediate, or frail — and 2 subgroups — frail or non-frail.
In the overall population, 396 patients were non-frail (53.3% of the D-Rd arm and 54.2% of the Rd arm), including 146 who were fit (18.5% and 21.1%, respectively) and 250 who were in the intermediate group (34.8% and 33.1%, respectively). The remaining 341 patients were frail (46.7% and 45.8%, respectively).
At a median follow-up of 36.4 months, D-Rd conferred a PFS benefit across the frail and non-frail subgroups.
In the fit subgroup, the median PFS was not reached in the D-Rd arm and was 41.7 months in the Rd arm (hazard ratio [HR], 0.41; P =.0028). In the intermediate subgroup, the median PFS was not reached in either treatment arm (HR, 0.53; P =.0024).
In the total non-frail subgroup, the median PFS was not reached in the D-Rd arm and was 41.7 months in the Rd arm (HR, 0.48; P <.0001). In the frail subgroup, the median PFS was not reached and 30.4 months, respectively (HR, 0.62; P =.003).
The 3-year PFS rate was higher in the D-Rd arm than in the Rd arm across all frailty subgroups:
- Fit — 78.3% with D-Rd and 53.6% with Rd
- Intermediate — 70.4% with D-Rd and 51.7% with Rd
- All non-frail — 73.2% with D-Rd and 52.1% with Rd
- Frail — 61.5% with D-Rd and 39.5% with Rd.
“The safety profile of D-Rd in frailty subgroups was generally consistent with the overall population of MAIA,” the researchers wrote.
The most common grade 3-4 treatment-emergent adverse event (TEAE) was neutropenia in both frail patients (57.7% with D-Rd and 33.1% with Rd) and non-frail patients (45.4% and 37.2%, respectively).
In both treatment arms, the frail patients had higher rates of grade 3-4 TEAEs, serious TEAEs, treatment discontinuation, and death.
The researchers concluded that these results “support the clinical benefit of D-Rd” in transplant-ineligible patients with newly diagnosed MM, regardless of frailty status.
Disclosures: This research was 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.
- Facon T, Cook G, Usmani SZ, et al. Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: Frailty subgroup analysis of MAIA. Leukemia. Published online January 2, 2022. doi:10.1038/s41375-021-01488-8
- Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019; 380:2104-2115. doi:10.1056/NEJMoa1817249