Daratumumab Plus Lenalidomide (D-R) Versus Lenalidomide (R) Alone As Maintenance Therapy in Newly Diagnosed Multiple Myeloma (NDMM) after Transplant: Analysis of the Phase 3 Auriga Study Among Clinically Relevant Subgroups
Authors: Foster Laahn , Anderson Larry D , Chung Alfred , Chaulagain Chakra , Pettijohn Erin M. , Cowan Andrew J. , Costello Caitlin , Larson Sarah M. , Sborov Douglas W. , Shain Kenneth H. , Silbermann Rebecca , Voorhees Peter M. , Krevvata Maria , Pei Huiling , Patel Sharmila , Khare Vipin , Cortoos Annelore , Carson Robin , Lin Thomas S. , Badros Ashraf Z. 
Published: December 2024

Introduction: Induction/consolidation and autologous stem cell transplant (ASCT) followed by R maintenance is standard therapy for transplant-eligible (TE) NDMM patients (pts). Daratumumab (DARA) is an anti-CD38 antibody approved as combination therapy for induction/consolidation treatment of TE NDMM. The phase 3 AURIGA study (NCT03901963) is the first randomized study to directly compare DARA-based maintenance therapy vs standard R maintenance therapy. Here, we present a post hoc analysis of clinically relevant subgroups from AURIGA by age (&lt;65 yrs, ≥65 yrs); race (Black, White); International Staging System (ISS) stage III disease; and cytogenetic high risk at diagnosis per the standard definition (del[17p], t[4;14], t[14;16]) and the revised definition (also including t[14;20] and gain/amp[1q21]).

Methods: Eligible pts with NDMM were 18-79 yrs of age, in very good partial response or better (≥VGPR) and positive for minimal residual disease (MRD [10-5]; NGS) following ASCT, anti-CD38 naïve, received ≥4 induction cycles, and enrolled within 12 months of start of induction therapy and 6 months of ASCT. Pts received 28-day cycles of R maintenance (10mg PO D1-28 [after C3, 15mg PO, if tolerated]) ± subcutaneous DARA (DARA SC; 1,800mg QW C1-2, Q2W C3-6, Q4W C7+) for up to 36 cycles or until disease progression, unacceptable toxicity, or withdrawal. Pts benefiting from DARA and/or R could continue treatment after the end of the study treatment period, per the investigator's discretion. The primary endpoint was MRD-negative (10-5) conversion rate by 12 months from start of maintenance therapy.

Results: 200 pts were randomized (D-R, n=99; R, n=101); subgroups had similar numbers of pts per arm: &lt;65 years (n=61; n=61), ≥65 yrs (n=38; n=40), Black (n=20; n=24), White (n=67; n=68), and at diagnosis: ISS stage III disease (n=23; n=23), normal (n=63; n=66) and high cytogenetic risk (n=22; n=15) per the standard definition, and normal (n=52; n=53) and high cytogenetic risk (n=32; n=30) per the revised definition. The MRD-negative (10-5) conversion rate by 12 months was consistently higher for D-R vs R across subgroups: &lt;65 yrs (49.2% vs 19.7%; odds ratio [OR], 3.95; 95% CI, 1.76-8.85), ≥65 yrs (52.6% vs 17.5%; OR, 5.24; 95% CI, 1.86-14.74); Black (60.0% vs 16.7%; OR, 7.50; 95% CI, 1.85-30.34); White (46.3% vs 20.6%; OR, 3.32; 95% CI, 1.55-7.10); ISS stage III (65.2% vs 13.0%; OR, 12.50; 95% CI, 2.83-55.25); normal (55.6% vs 21.2%; OR, 4.64; 95% CI, 2.15-10.04) and high cytogenetic risk per the standard definition (31.8% vs 6.7%; OR, 6.53; 95% CI, 0.71-60.05); and normal (53.8% vs 22.6%; OR, 3.99; 95% CI, 1.72-9.26) and high cytogenetic risk per the revised definition (43.8% vs 13.3%; OR, 5.06; 95% CI, 1.43-17.88). At 32.3 months of median follow-up, PFS hazard ratio (HR) point estimates among subgroups consistently favored D-R vs R: &lt;65 yrs (HR, 0.51; 95% CI, 0.22-1.18), ≥65 yrs (HR, 0.71; 95% CI, 0.30-1.67); Black (HR, 0.66; 95% CI, 0.16-2.75); White (HR, 0.56; 95% CI, 0.28-1.12); ISS stage III (HR, 0.26; 95% CI, 0.08-0.85); normal (HR, 0.59; 95% CI, 0.23-1.49) and high cytogenetic risk per the standard definition (HR, 0.60; 95% CI, 0.21-1.70); and normal (HR, 0.69; 95% CI, 0.24-1.95) and high cytogenetic risk per the revised definition (HR, 0.53; 95% CI, 0.21-1.31). Additional data in other high-risk subgroups, including 1q21 abnormalities, will be presented.

The incidence of grade 3/4 TEAEs was higher for D-R vs R for both Black (D-R, 75.0% [15/20]; R, 66.7% [16/24]) and White (76.6% [49/64]; 70.8% [46/65]) pts. Grade 3/4 TEAEs occurred more frequently for D-R vs R in pts &lt;65 yrs (D-R, 76.3% [45/59]; R, 63.8% [37/58]), and were similar for D-R vs R in pts ≥65 yrs (70.3% [26/37]; 72.5% [29/40]). Grade 3/4 infection rates for D-R vs R among subgroups were: Black (D-R, 20% [4/20]; R, 20.8% [5/24]); White (20.3% [13/64]; 12.3% [8/65]); &lt;65 yrs (18.6% [11/59]; 10.3% [6/58]); ≥65 yrs (18.9% [7/37]; 17.5% [7/40]).

Conclusion: This post hoc analysis of AURIGA showed that addition of DARA to R maintenance demonstrated improvement across clinically relevant subgroups in MRD-negative conversion rate by 12 months from the start of maintenance as well as PFS. Grade 3/4 TEAEs were higher for D-R vs R in Black and White pts, as well as those &lt;65 yrs. These results demonstrate the benefit of adding DARA to R maintenance in clinically relevant subgroups of anti-CD38 naïve pts with NDMM who were positive for MRD post-ASCT.