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 center dot 1%, and 3 center dot 6, 8 center dot 1 and 11 center dot 9 months, respectively. Refractoriness to carfilzomib and/or lenalidomide, and neutropenia (<1.0 x 10(9)/l) resulted in poorer ORRs. An Eastern Cooperative Oncology Group Performance Status of >= 3, neutropenia (<1.0 x 10(9)/l), thrombocytopenia (<75 x 10(9)/l), and renal failure (glomerular filtration rate of <20 ml/min/1 center dot 73 m(2)) 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 center dot 823 and 3 center dot 677, all P < 0 center dot 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 center dot 1% vs. 4 center dot 3%; P = 0 center dot 099). Despite failure of DM, subsequent therapy with pomalidomide-based therapy or carfilzomib-dexamethasone provided a 66 center dot 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.

Automated summary

Real-world outcomes of daratumumab monotherapy for relapsed/refractory multiple myeloma showed favorable responses, but certain factors related to trial-unfitness may offset its efficacy. Patients in the modified trial-unfit group had poorer survival outcomes, indicating the potential impact of specific characteristics on treatment efficacy.