Prognostic factors for patients with relapsed or refractory multiple myeloma who are initiating a fourth or later line car T-cell or bispecific antibody therapy: a systematic literature review and meta-analysis

INTRODUCTION: Multiple myeloma is associated with substantial disease burden and frequent relapses, despite therapeutic advances. As the rapidly evolving evidence base for chimeric antigen receptor (CAR) T-cell and bispecific antibody (BsAb) therapies is dominated by single-arm trials and real-world studies, decision-makers increasingly rely on understanding key prognostic factors (i.e. demographic and clinical characteristics associated with outcomes) to inform indirect treatment comparisons (ITCs). METHODS: Guided by a targeted review and clinician input to identify factors of interest, we systematically searched MEDLINE, EMBASE, CENTRAL, and pertinent conferences for trials and observational studies evaluating CAR T-cell and/or BsAb therapies. Eligible studies presented potential factors in relation to efficacy, survival, and/or safety outcomes. Meta-analyses summarized factor-outcome associations, overall and by treatment class. RESULTS: From 102 publications (43 studies), analyses were feasible for 15 potential factors. Several statistically significant factor-outcome dyads were identified, including factors of age, cytogenetic risk, ECOG PS, ISS/R-ISS stage, bone marrow plasma cell burden, extramedullary disease, ferritin, prior anti-BCMA exposure, and triple-class refractory status. Associations varied by outcome and, in some cases, by treatment class. CONCLUSIONS: This study highlights prognostic factors, identified through a systematic and transparent process, that may influence ITCs and policy decision-making in later-line multiple myeloma. REGISTRATION: This Systematic Literature Review and Meta-Analysis was prospectively registered with PROSPERO (CRD42023446880). Only pilot work and no formal review or data collection occurred prior to the registration.