Predictive and Prognostic Significance of Patient-Reported Outcomes for Survival and Adverse Events in Daratumumab-Treated Multiple Myeloma

Abstract

Objectives: Patient-reported outcomes (PROs), including physical function, have predictive potential for survival but remain underexplored in multiple myeloma (MM). This study evaluates the predictive and prognostic value of PROs for treatment outcomes in MM patients on daratumumab-based therapy and evaluates physical function versus ECOG Performance Status as a potential treatment-effect modifier. Methods: Data was pooled from randomized trials (MAIA, POLLUX, CASTOR) that collected pretreatment PROs using EORTC QLQ-C30. Cox models and logistic regression examined associations between PROs and overall survival (OS), progression-free survival (PFS) and grade ≥ 3 adverse events. Physical function versus ECOG-PS was examined as a treatment effect modifier for daratumumab versus non-daratumumab therapies. Results: Among 1804 patients, 1535 (85%) had pretreatment PROs. Physical function, global health, and fatigue were most prognostic for survival and adverse events. Physical function provided independent prognostic value beyond ECOG-PS and was predictive of treatment effect. Low physical function patients experienced greater OS treatment benefit (adjusted HR (aHR) [95% CI] 0.53 [0.40–0.70], p interaction = 0.02) and PFS (aHR [95% CI] 0.30 [0.30–0.48], p interaction = 0.03) from daratumumab versus high-physical function (OS aHR 0.86 [0.62–1.19], PFS aHR 0.53 [0.42–0.67]). Conclusion: Physical function is a predictive and prognostic marker that complements ECOG-PS, supporting its use in informing therapy decisions for daratumumab-based treatments.