ATLAS phase III: KRd vs lenalidomide maintenance after auto-HSCT in NDMM

Results from ATLAS (NCT02659293), a multicenter, open-label, randomized, phase III trial, evaluating carfilzomib + lenalidomide + dexamethasone (KRd; n = 92) vs lenalidomide alone (n = 88) as maintenance therapy, incorporating a measurable residual disease (MRD)-guided de‑escalation strategy, after autologous hematopoietic stem cell transplantation (auto-HSCT) in adults with newly diagnosed multiple myeloma (NDMM) and at least stable disease, were published in The Lancet Haematology by Dytfeld et al. The primary endpoint was progression-free survival (PFS). 

Key data: With a median follow-up of 69 months, 4-year PFS was 67.5% with KRd vs 38.0% with lenalidomide (p < 0.0001); median PFS was longer with KRd (72.8 months vs 37.3 months; hazard ratio [HR], 0.46; p = 0.0002). Median overall survival (OS) was not reached with KRd vs 82.2 months with lenalidomide (HR, 0.49; p = 0.020). MRD negativity rates at best response were higher with KRd vs lenalidomide (73% vs 48%; p = 0.0007). No new safety signals were observed.  

Key learning: KRd demonstrated superior PFS and evidence of improved OS, though not a predefined endpoint, compared with lenalidomide alone after auto-HSCT in NDMM, supporting MRD-adapted maintenance intensification in this setting.