Daratumumab monotherapy for relapsed/refractory multiple myeloma, focussed on clinical trial-unfit patients and subsequent therapy.

Real-world outcomes of daratumumab monotherapy (DM) for relapsed/refractory multiple myeloma (RRMM) have remained unclear. We conducted a multicentre retrospective study of 107 patients receiving DM for RRMM. The cohort included 64 trial-unfit patients whose characteristics could not meet inclusion criteria in two previous clinical trials (GEN501 and SIRIUS). The overall response rate (ORR), and median first and second progression-free survival (PFS1 and PFS2) and overall survival were 42·1%, and 3·6, 8·1 and 11·9 months, respectively. Refractoriness to carfilzomib and/or lenalidomide, and neutropenia (<1.0 × 10 /l) resulted in poorer ORRs. An Eastern Cooperative Oncology Group Performance Status of ≥3, neutropenia (<1.0 × 10 /l), thrombocytopenia (<75 × 10 /l), and renal failure (glomerular filtration rate of <20 ml/min/1·73 m ) were associated with poor PFS1 and PFS2 in respective univariate analysis. The modified trial-unfit group, based on the above factors, showed significantly negative impacts on PFS1 and PFS2 (hazard ratio 2·823 and 3·677, all P < 0·001) in multivariate analysis despite having a 34% ORR. Fatal infections occurred more often in the modified trial-unfit group than in the others (16·1% vs. 4·3%; P = 0·099). Despite failure of DM, subsequent therapy with pomalidomide-based therapy or carfilzomib-dexamethasone provided a 66·6% ORR. Real-world DM showed favourable efficacies for RRMM and, potentially, additional benefits with subsequent therapies. However, characteristics corresponding with trial-unfitness might offset the efficacy of DM.