Daratumumab for newly diagnosed multiple myeloma: Pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS.

Background: Older adults with newly diagnosed multiple myeloma (NDMM) have poor prognosis and constitute a subgroup of particular interest. In the GRIFFIN (NCT02874742) and PERSEUS (NCT03710603) studies, adding daratumumab to bortezomib/lenalidomide/dexamethasone (VRd) induction/consolidation and lenalidomide (R) maintenance deepened responses and improved progression-free survival (PFS) versus VRd/R in transplant-eligible patients with NDMM. Subgroup analyses of patients aged ≥65 years in PERSEUS demonstrated less pronounced PFS benefits (HRs: 0.97 [computerized algorithm]; 0.87 [independent review committee (IRC)]), potentially due to small event numbers, cytogenetic risk imbalances (high risk: D-VRd, 25.5%; VRd, 19.5%), and specific censoring rules. Here, we report results from a post hoc, pooled analysis of GRIFFIN and PERSEUS in patients aged ≥65 years (D-VRd, n = 122; VRd, n = 115).

Methods: Using patient-level data, PFS analysis was evaluated per computerized algorithm in GRIFFIN and IRC in PERSEUS, stratified by International Staging System stage and cytogenetic risk, with no censoring of PFS events after ≥2 missing disease evaluations.

Results: At a median follow-up of 49.6/47.5 months (GRIFFIN/PERSEUS), a trend in improved PFS was seen among patients aged ≥65 years favoring D-VRd (HR, 0.56 [95% CI, 0.30-1.01]). D-VRd improved rates of complete response or better (82.8% vs. 67.0%; OR, 2.37 [95% CI, 1.28-4.39]; P = .0046) and minimal residual disease negativity (10; 66.4% vs. 41.7%; OR, 2.75 [95% CI, 1.61-4.71]; P = .0002) versus VRd. No new safety concerns were identified.

Conclusion: These data support use of D-VRd followed by D-R maintenance as standard of care for all transplant-eligible patients with NDMM, regardless of age up to 70 years.