From toxicity to immunity: Evaluating CAR-T and conventional therapies in multiple myeloma through quality-adjusted life year (QALY) outcomes

Multiple myeloma (MM) remains characterized by recurrent relapse and cumulative treatment burden despite major therapeutic advances. This study compared conventional stepwise regimens with CAR-T cell therapy in terms of QoL, toxicity, cost, and ethical considerations within a model-based comparative framework. This comparative pharmacoeconomic modeling analysis was based on published clinical trial data. Kaplan-Meier survival curves were digitized to estimate mean overall survival (OS) and progression-free survival (PFS) using area-under-the-curve integration. Treatment costs were calculated based on published pricing and trial-derived treatment durations. A simple and transparent ECOG-based utility model was developed to enable clinicians, researchers, and health policy authorities to estimate quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) across regimens spanning heterogeneous treatment lines. The present analysis synthesizes outcome data from 19 pivotal trials and real-world cohorts (N = 7,793 patients). Among heavily pretreated patients, CAR-T therapy approximately doubled OS and PFS compared with other late-line regimens and yielded higher QALY estimates with lower cumulative treatment burden. Daratumumab-based combinations improved outcomes but reached very high costs (∼USD 1 million/patient), while carfilzomib-based regimens remained costly but clinically important for high-risk disease. VMP represented a practical lower-cost option for transplant-ineligible or resource-limited patients. In treatment-line–stratified analysis, later-line/RRMM regimens had higher median ICER-equivalent values than early-line/induction regimens (USD 739,050/QALY vs USD 218,687/QALY; 3.4-fold higher), whereas CAR-T regimens showed a median ICER-equivalent estimate of USD 299,723/QALY, approximately 2.5-fold lower than later-line/RRMM conventional regimens. Within this model-based comparative framework, CAR-T provided substantial survival and quality-adjusted outcome gains after three or more prior therapy lines, with promising potential for earlier use. Despite its upfront single-payment structure, CAR-T did not show a disproportionate ICER-equivalent burden compared with later-line conventional regimens. However, limited global availability raises ethical concerns regarding access, infrastructure, reimbursement, and equity. Further studies incorporating longer follow-up and patient-level QoL data are needed to refine its role in multiple myeloma care.