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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 (\u223cUSD 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\u2013stratified 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.<\/jats:p>","DOI":"10.1177\/20406207261484713","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:00:51Z","timestamp":1788458451000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["From toxicity to immunity: Evaluating CAR-T and conventional therapies in multiple myeloma through quality-adjusted life year (QALY) outcomes"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5367-6687","authenticated-orcid":false,"given":"Guluzar Gulnur","family":"Itez","sequence":"first","affiliation":[{"name":"Ankara University"},{"name":"Institute of Health Sciences"},{"name":"Ankara University"},{"name":"Stem Cell Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7693-0958","authenticated-orcid":false,"given":"Asuman","family":"Sunguro\u011flu","sequence":"additional","affiliation":[{"name":"Ankara University"},{"name":"Institute of Health Sciences"},{"name":"Ankara University"},{"name":"Stem Cell Institute"},{"name":"Ankara University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27422"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14051655"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hon.70067"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2024.11.012"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_200869"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040625"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04651-w"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000970380.84060.bf"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-024-01191-8"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-021-00254-w"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115888"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-025-01330-9"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2303379"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2023-0954"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-078022"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.974038"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.11.011"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(25)00018-X"},{"key":"e_1_3_7_20_2","article-title":"Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study","author":"Lee JH","unstructured":"Lee JH, Choi J, Min C-K, et al. 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