Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Transplant-Ineligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Clinical Assessment of Key Subgroups of the Phase 3 Maia Study

Abstract

Introduction: The MAIA study (NCT02252172) evaluated D-Rd versus Rd alone in transplant-ineligible pts with NDMM. At a median follow-up of 56.2 months, D-Rd significantly improved progression-free survival (PFS) and overall survival versus Rd (Facon T, Lancet Oncol 2021). Here, we present an analysis of clinically important subgroups in MAIA, including pts aged ≥75 years, pts with International Staging System (ISS) stage III disease, pts with renal insufficiency (defined as baseline creatinine clearance [CrCl] ≤60 mL/min), pts with extramedullary plasmacytomas at baseline, and pts with high cytogenetic risk (defined as having ≥1 of the following high-risk cytogenetic abnormalities: t[4;14], t[14;16], del17p [per IMWG recommendations]). Methods: In MAIA, pts with NDMM who were ineligible for high-dose chemotherapy and autologous stem-cell transplant were randomized 1:1 to receive D-Rd or Rd. All pts received 28-day cycles of oral Rd (R: 25 mg [10 mg recommended if CrCl was 30-50 mL/min] on Days 1-21; d: 40 mg [20 mg if aged >75 years or body-mass index <18.5 kg/m2] on Days 1, 8, 15, 22). Pts in the D-Rd arm received intravenous daratumumab (16 mg/kg QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter). Pts in both arms were treated until disease progression or unacceptable toxicity. The primary endpoint was PFS, and key secondary endpoints included overall response rate (ORR) and minimal residual disease (MRD)-negativity rate (10-5 sensitivity). Results: 737 pts were randomized (D-Rd, n=368; Rd, n=369); most subgroups had a similar number of pts per treatment arm: age ≥75 years (n=160; n=161); ISS stage III (n=107; n=110); renal insufficiency (n=162; n=142); extramedullary plasmacytomas (n=15; n=9); and high cytogenetic risk (n=48; n=44). After a 64.5-month median follow-up, PFS (Figure A) and ORR (Figure B) generally favored D-Rd versus Rd across subgroups. MRD-negativity rates were higher with D-Rd versus Rd for pts aged ≥75 years (26.9% vs 9.9%; P<0.0001), pts with ISS stage III disease (27.1% vs 10.9%; P=0.0030), pts with renal insufficiency (29.6% vs 7.7%; P<0.0001), pts with extramedullary plasmacytomas (33.3% vs 0%; P=0.1181), and pts with high cytogenetic risk (25.0% vs 2.3%; P=0.0019). Sustained (≥6 months and ≥12 months) MRD-negativity rates were higher with D-Rd versus Rd across subgroups: age ≥75 years (≥6 months, 15.6% vs 5.0%; ≥12 months, 13.8% vs 3.1%), ISS stage III disease (≥6 months, 17.8% vs 3.6%; ≥12 months, 15.9% vs 2.7%), renal insufficiency (≥6 months, 21.0% vs 1.4%; ≥12 months, 18.5% vs 1.4%), extramedullary plasmacytomas (≥6 months, 26.7% vs 0%; ≥12 months, 13.3% vs 0%), and high cytogenetic risk (≥6 months, 12.5% vs 0%; ≥12 months, 12.5% vs 0%). In an analysis of safety among pts aged ≥75 years, grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 95.5% of D-Rd pts and 95.0% of Rd pts; the most common (≥20%; D-Rd/Rd) were neutropenia (62.4%/41.5%), lymphopenia (21.0%/12.6%), anemia (20.4%/25.2%), and pneumonia (20.4%/14.5%). Serious TEAEs occurred in 80.9% and 79.2% of D-Rd and Rd pts, respectively. TEAEs led to study treatment discontinuation in 15.3% of D-Rd pts and 27.7% of Rd pts. TEAEs with an outcome of death occurred in 11.5% of D-Rd pts and 13.2% Rd pts. Conclusions: In this subgroup analysis of MAIA, D-Rd improved PFS, ORR, and MRD-negativity rates versus Rd across clinically important subgroups, including pts aged ≥75 years, pts with ISS stage III disease, pts with renal insufficiency, pts with extramedullary plasmacytomas, and pts with high cytogenetic risk. In pts aged ≥75 years, the rates of grade 3/4 and serious TEAEs were similar with D-Rd and Rd, with a lower rate of discontinuation due to TEAEs for D-Rd versus Rd. Results for these clinically important subgroups provide confidence in using D-Rd across all pt types, supporting D-Rd as a standard of care for transplant-ineligible pts with NDMM. Results for additional cytogenetic risk subgroups that include pts with gain and/or amp 1q21 will be presented at the meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal