P-363: Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Transplant-eligible Patients With Multiple Myeloma: A Pooled Analysis of Patients Aged ≥65 Years From Both PERSEUS and GRIFFIN Studies

Introduction: In the PERSEUS and GRIFFIN studies, adding daratumumab (DARA) to bortezomib/lenalidomide/dexamethasone (D-VRd) induction/consolidation (ind/consol) and R (D-R) maintenance (maint) resulted in deep responses and improved PFS vs VRd/R in transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM). Pts ≥65 yrs of age constitute a group whose outcome is of particular interest. In PERSEUS among pts aged ≥65 yrs, PFS hazard ratios (HRs) were 0.97 (computerized algorithm [comp alg]) and 0.87 (Independent Committee Review [IRC]), potentially due to small numbers of events, cytogenetic risk imbalances (high risk: D-VRd 25.5%; VRd 19.5%), and censoring of pts for PFS after ≥2 missing consecutive disease evaluations (events censored: D-VRd, 0; VRd, 3). However, other randomized studies have shown the benefit of DARA in older pts, including GRIFFIN with D-VRd. To better understand the effect of DARA in combination with VRd in older pts with TE NDMM we performed a post hoc, pooled analysis of PERSEUS and GRIFFIN in pts aged ≥65 yrs.

Methods: In both studies, TE pts with NDMM aged 18-70 yrs were randomized 1:1 to D-VRd or VRd. Pts received 4 ind cycles (PERSEUS 28-day cycles/GRIFFIN 21-day cycles) and 2 post-ASCT consol cycles of VRd, then R maint. Pts randomized to D-VRd also received DARA during ind/consol and maint. In this post hoc analysis, PFS data was used from comp alg in GRIFFIN and IRC in PERSEUS, and HRs and 95% CIs were estimated using a Cox regression model stratified by ISS disease stage and cytogenetic risk, with no censoring of PFS events after ≥2 missing disease evaluations. Pooled analyses were conducted in pts aged ≥65 yrs.

Results: Pts aged ≥65 yrs represented 25.5% of pts in PERSEUS (D-VRd, 94/355; VRd, 87/354) and 27.1% of pts in GRIFFIN (D-VRd, 28/104; VRd, 28/103). Among pts aged ≥65 yrs, 9.0% in D-VRd and 13.0% in VRd had ISS stage III disease and 22.7% and 19.3% had high-risk cytogenetics. Median PFS was not reached in either treatment group or study. Stratified by ISS and cytogenetic risk and not censoring pts on basis of 2 consecutive missing disease assessments, PFS HRs favored D-VRd in PERSEUS (HR 0.61 [95% CI 0.32-1.14]), GRIFFIN (HR 0.33 [95% CI 0.06-1.76]), and the pooled dataset (HR 0.56 [95% CI 0.31-1.01]). Rates of MRD neg (10^–5) were also higher with D-VRd vs VRd in PERSEUS (67.0% vs 49.4%; OR 2.08 [95% CI 1.14-3.79]), GRIFFIN (64.3% vs 17.9%; OR 6.40 [95% CI 1.80-22.75]), and the pooled dataset (66.4% vs 41.7%; OR 2.75 [95% CI 1.61-4.71]). Data on sustained (≥12 mo) MRD and overall response (IMWG), including complete response or better, will be presented. No new safety concerns were identified in pts aged ≥65 yrs.

Conclusions: D-VRd ind/consol and D-R maint led to improved PFS and MRD neg vs VRd/R in TE NDMM pts aged ≥65 yrs. These data support D-VRd/D-R as a standard of care and highlight the benefit of DARA during ind/consol and maint for all TE pts with NDMM, regardless of age.