OBJECTIVES: To evaluate the relationship between PFS and patient-reported symptoms (as measured by validated health-related quality of life [HRQoL] scores) among RRMM patients.

METHODS: A pre-defined literature review of patient preference studies was performed, which identified pain and fatigue as the most common symptoms of concern within RRMM; the relevance of pain/fatigue was confirmed by three clinical experts in MM. Consequently, ‘pain’ and ‘fatigue’ domains of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 were selected, in addition to the ‘disease symptoms’ domain of the QLQ-MY20 that assesses pain in different locations. We analyzed the change from baseline in each symptom domain jointly with PFS assuming a current slope association structure. For each symptom domain (separately), we evaluated trial-specific joint models based on individual patient data from six RRMM clinical trials, including four randomized controlled trials (OPTIMISMM, ELOQUENT-2, MM-003, and KarMMa-3) and two phase II single-arm trials (KarMMa and CC-220-MM-001). Covariates were selected based on study design/stratification factors, clinical input, and literature reviews of RRMM HRQoL prognostic factors. Estimates from the joint models were compared to each of the submodels separately (i.e., longitudinal linear mixed effects for each symptom domain and Cox proportional hazards for PFS).

RESULTS: Deterioration in pain/fatigue was consistently associated with an increased hazard of PFS events (disease progression or death) based on the direction of the hazard ratios (HRs) (i.e. HR>1) across the trial-specific joint models. Joint model HRs were statistically significant (p<0.05) for pain (OPTIMISMM, MM-003, CC-220-MM-001, KarMMa, KarMMa-3), disease symptoms (OPTIMISMM, MM-003, CC-220-MM-001, KarMMa-3), and fatigue (OPTIMISMM, ELOQUENT-2, MM-003, CC-220-MM-001, KarMMa-3) (HRs range: 1.00-1.32).

CONCLUSIONS: Pain and fatigue were associated with an increased hazard of disease progression or death among RRMM patient populations, suggesting that PFS is associated with MM-relevant symptom worsening and is therefore meaningful from the patient perspective.