Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center

PLOS ONE RESEARCH ARTICLE Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center Sérgio Chacim1,2☯, Teresa Monjardino ID3☯*, José Luı́s Cunha4,5, Pedro Medeiros4,5,6, Patrı́cia Redondo4,5, Maria José Bento3,7,8, José Mário Mariz1 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Chacim S, Monjardino T, Cunha JL, Medeiros P, Redondo P, Bento MJ, et al. (2022) Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center. PLoS ONE 17(12): e0278950. https://doi.org/10.1371/ journal.pone.0278950 Editor: Yasunori Sato, Keio University School of Medicine, JAPAN Received: June 28, 2022 Accepted: November 24, 2022 Published: December 9, 2022 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0278950 Copyright: © 2022 Chacim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Due to imposition by the Data Protection Officer from Portuguese Oncology Institute of Porto (IPO-Porto), data from 1 Department of Onco-hematology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal, 2 Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto Research Center (CIIPOP) / RISE@CI-IPOP (Health Research Network) / Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal, 3 Cancer Epidemiology Group, Portuguese Oncology Institute of Porto Research Center (CIIPOP) / RISE@CI-IPOP (Health Research Network) / Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal, 4 Outcomes Research Lab, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal, 5 Management, Outcomes Research, and Economics in Healthcare Group, Portuguese Oncology Institute of Porto Research Center (CI-IPOP) / RISE@CI-IPOP (Health Research Network) / Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal, 6 Medicine and Oncological Medicine Departments Management, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal, 7 Department of Epidemiology, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal, 8 Department of Population Studies, ICBAS-School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, Portugal ☯ These authors contributed equally to this work. * Abstract Real world effectiveness, toxicity and costs analyses from chimeric antigen receptor (CAR)T cell therapy are of utmost relevance to determine whether and how to offer patients highly personalized immunotherapy. In this study, we aimed at describing CAR T-cells effectiveness, safety and costs in a Portuguese Comprehensive Cancer Center. We performed a retrospective descriptive study of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma and transformed follicular lymphoma referred to CAR T-cell therapy, between May 2019 and February 2021. Rates of treatment response, toxicity and survival (Kaplan-Meier method) were analyzed by intention-to-treat. Direct medical costs stratified by inpatient-care, outpatient-care, and diagnostic-therapeutic procedures (DTP) were derived based on resources used and their respective unit costs. In twenty patients (median age 49.5y; 55%male; 70%DLBCL; 50% with primary refractory disease), best overall and complete response rates were 65.0% and 45.0%, respectively. Median overall (OS) and progression-free survivals were 9.2 and 7.3 months; 12-month OS rate was 42.6% (95%CI:23.2–78.3). Grade�3 cytokine release syndrome and neurotoxicity occurred in 5.6% and 11.1% of patients, respectively. CAR T-cell therapy expenditure, including adverse events costs, was 7 176 196€, or 286 238€ when excluding drug cost. Median cost for treated patient was 355 165€ with CAR T-cell drug cost accounting for 97.0% of the overall expense. Excluding CAR T-cell acquisition cost, PLOS ONE | https://doi.org/10.1371/journal.pone.0278950 December 9, 2022 1 / 14 PLOS ONE this study is only available upon request due to legal and ethical restrictions on sharing data publicly. IPO-Porto Data Protection Officer provided the following explanation: “This study is based on a very small sample (n=20), so we understand that the particularity of this study, given the current state of the art, may lead to an increased risk of violating the privacy of our patients through a possible identification of the data subject. However, this concern is the result of the ethical and legal obligations to which our institution is bound in light of the current guidelines and recommendations and legislation”. Data requests may be sent to the Data Protection Officer () and to the Department of Onco-hematology at IPO-Porto (s. ). Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. CAR T-cell therapy in a real world setting inpatient-care and DTP accounted for 57% and 38% of total cost/patient, respectively. Our findings highlight the heavy economic burden of CAR T-cell therapy driven by drug acquisition costs. Introduction Chimeric antigen receptor (CAR)-T cells represent a new class of cancer immunotherapies that genetically engineer patient T-cells to target their disease [1, 2]. Results from CAR T-cells clinical trials and real-life evidence have shown high rates of durable remissions responses and meaningful overall survival benefits in relapsed/refractory large B-cell lymphomas [3–10]. However, these therapies are priced amongst the most expensive cancer therapies to date with list prices of approximately $373 000 US dollars in US and 320 000€ in Europe [11]. In addition to direct costs of acquisition and infusion of CAR T-cells, lymphodepletion, outpatient visits and exams, there are also costs attributable to hospitalization, intensive care unit (ICU) admissions, laboratory activity, imaging studies, specialized and multidisciplinary teams work and management of potentially life-threatening adverse effects [11–18]. Nevertheless, substitution effects may reduce the financial impact or CAR T-cell therapy, avoiding current futile treatments, potentially reducing autologous and allogenic stem cell transplantation for relapsed patients. Formal assessment of these aspects will improve knowledge about this technology, effective economic evaluation and understanding its real cost [11, 19, 20]. To date, scarce research has quanti (...truncated)