OBJECTIVES:  It is unclear whether the conceptual coverages of the instruments available to evaluate the health-related quality of life (HRQoL) of multiple myeloma (MM) patients are adequate in the relapsed or refractory (R/R) setting, with respect to the FDA’s patient-reported outcome (PRO) guidance.  To address this uncertainty, we conducted qualitative interviews with R/R MM patients and compared the results to the conceptual frameworks of three existing instruments. METHODS:  Two consecutive sets (n=15 and n=8) of qualitative concept elicitation (CE) interviews were conducted with R/R MM patients in the U.S.  The concepts reported were compared with the conceptual frameworks of the EORTC QLQ-C30 and QLQ-MY20, FACT-MM, and MDASI-MM.  In addition, a conceptual model was devised based on the results of these interviews, and an analysis of the relative timing (with respect to treatment/disease course) of the reported symptoms and impacts was conducted. RESULTS:  A total of 23 R/R MM patients (age range=50 to 89 years; mean age=66.7±10.1 years; male=56.5%) participated in the CE interviews. A total of 37 symptom concepts and 55 HRQoL impacts were reported.  Of the six symptom concepts reported by >2 patients, five (83.3%) were covered by the QLQ-C30 and MY-20, three (50.0%) by the FACT-MM, and three (50.0%) by the MDASI-MM.  Of the 23 impacts reported by >2 patients, 14 (60.9%) were covered by the QLQ-C30 and MY-20, 9 (39.1%) by the FACT-MM, and 7 (30.4%) by the MDASI-MM.  Analysis of the timing of symptom/impact reporting revealed that the majority of concepts noted by >2 MM patients were present both pre- and post-relapse. CONCLUSIONS:  These findings indicate that the EORTC QLQ-C30 and QLQ-MY20 instruments are appropriate for capturing the symptom and impact domains most often reported by R/R MM patients, although room may remain for improvement in assessing functional impacts at the conceptual level in this population.