-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3659 Global Access to Chimeric Antigen Receptor (CAR) T-Cell Therapies: Health Technology Assessment (HTA) of CAR T in G7 Countries and Australia

Program: Oral and Poster Abstracts
Session: 902. Health Services and Quality Improvement: Lymphoid Malignancies: Poster II
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality)
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Alex Y Ge, MD1*, William B Feldman, MD, DPhil, MPH2,3*, Martin F Kaiser, MD4, Kai Rejeski, MD5,6, Gloria Iacoboni, MD7*, Michael J Dickinson, MBBS, DMedSci, FRACP, FRCPA8,9, Aaron S Kesselheim, MD, JD, MPH3* and Edward R Scheffer Cliff, MBBS, MPH8,10,11

1Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA
2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
3Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
4The Institute of Cancer Research, London, ENG, United Kingdom
5Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
6Department of Medicine III, LMU University Hospital, LMU Munich, Munich, Germany
7Department of Hematology, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Universitat Autònoma of Barcelona (UAB), Barcelona, Spain
8Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia
9Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia
10Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
11Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia

Introduction

CAR T-cells represent a major treatment advance for certain patients with hematologic malignancies. Barriers to accessing this technology include its prohibitive cost, the autologous nature of CAR T-cells (which necessitates a delay between apheresis and infusion), and the need for a specialized manufacturing process requiring a sophisticated logistical infrastructure. In countries outside the US, decisions to reimburse therapies depend on formal evaluations by health technology assessment (HTA) bodies, which account for factors including clinical benefits and comparative effectiveness. Cost-effectiveness studies of CAR T-cells have found mixed results. Given the high price of CAR T-cell therapies, we hypothesized that their variable efficacy and cost-effectiveness would affect HTA decision-making and reimbursement decisions. We also hypothesized that reimbursement decisions would differ between clinical settings for which there is demonstrated curative potential (e.g., DLBCL) versus those for which the therapy does not yet appear to be curative (e.g., myeloma).

Methods

To address these questions, we performed a cross-sectional analysis of reimbursement decisions made by HTA bodies of the G7 countries and Australia for all CAR T-cell indications approved in the US through January 1, 2024. We used the FDA and National Comprehensive Cancer Network websites to define the full set of drug-indication pairs and obtained corresponding full-form HTA reports from the websites of each HTA body. From each report, we abstracted (1) the CAR T-cell product and indication for use, (2) final reimbursement decision, and (3) factors used to justify HTA decision-making. For drug-indication pairs with multiple HTA evaluations, the most recent HTA decision prior to January 1, 2024 was used to determine reimbursement status. For Germany and Japan, where HTA bodies are utilized for price negotiations following drug approval and do not provide reimbursement recommendations per se, drug approval was used to infer reimbursement status. Drugs recommended with conditional clinical requirements were considered reimbursed.

Results

We identified 6 CAR T-cell products linked to 12 indications approved by the FDA through January 1, 2024. Of the 84 drug-indication pairs across countries (excluding the US), 59 (70%) were recommended for reimbursement, 8 (10%) were not recommended for reimbursement following an HTA evaluation, and 17 (20%) were non-reimbursed for other reasons (e.g., an application was never submitted). Countries with the most recommendations for funding were France and Germany (11, 92%). Japan recommended reimbursement for 9 (75%) indications, while Italy and Canada did for 8 (67%). Countries with the fewest reimbursed indications included England (6, 50%) and Australia (4, 33%). The most recommended drug-indication pair was axicabtagene ciloleucel (axi-cel) for DLBCL after two or more lines of systemic therapy, the only drug-indication pair to be approved in all countries. The fewest recommendations were linked to idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) for myeloma as fifth or later line treatment, and lisocabtagene maraleucel for DLBCL relapsed or refractory to first-line therapy. For HTA bodies that provided rationale for drug reimbursement decisions, an analysis identified (1) inadequate comparator arms, (2) a lack of long-term survival data, (3) uncertainty regarding the true magnitude of clinical benefit, and (4) cost-effectiveness as common themes for recommendation against reimbursement.

Discussion

Despite cited concerns regarding cost-effectiveness and disparities in access, we find that the majority of CAR T-cell indications were recommended for reimbursement in this sample of the highest-income countries (HICs) globally. Among the CAR-Ts, HICs most frequently provided reimbursement for axi-cel for DLBCL (the only indication with demonstrated overall survival benefit) and least often provided reimbursement for ide-cel and cilta-cel for myeloma (for which CAR-T cells do not yet appear to have curative potential, though this may be one of multiple reasons). Our results demonstrate that HTA decisions are not necessarily the bottleneck in the HICs for access to CAR-T among patients for which the data indicate the greatest therapeutic potential, and that approaches are heterogeneous between jurisdictions.

Disclosures: Kaiser: Regeneron: Consultancy; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy; Pfizer: Consultancy, Honoraria; J&J/Janssen: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; GSK: Consultancy; Roche: Consultancy; Poolbeg: Consultancy, Honoraria. Rejeski: BMS/CELGENE: Consultancy, Honoraria; Pierre-Fabre: Other: Travel Support; Novartis: Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel Support, Research Funding. Iacoboni: BMS: Consultancy, Honoraria; AstraZeneca: Honoraria, Other: Travel support; AbbVie: Honoraria, Other: Travel Support; Novartis: Honoraria; Miltenyi: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; Autolus: Consultancy; Autolus, Bristol-Myers Squibb, Kite/Gilead, Miltenyi, Novartis: Consultancy; AbbVie, AstraZeneca, Autolus, Bristol-Myers Squibb, Kite/Gilead, Miltenyi, Novartis, Lilly and Sandoz: Honoraria; AbbVie, AstraZeneca, Kite/Gilead, Miltenyi: Other: Travel support. Dickinson: Takeda: Research Funding; MSD: Honoraria, Research Funding; Amgen: Honoraria; BMS/Celgene: Honoraria, Research Funding; Janssen: Honoraria; Gilead Sciences: Honoraria; Roche: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

*signifies non-member of ASH