Highlights
CAR T-cell therapies represent a transformative approach to treating relapsed or refractory hematologic malignancies, yet global access remains highly inequitable. This cross-sectional analysis of health technology assessment (HTA) bodies across G20 nations reveals that fewer than half of approved CAR T-indication pairs receive positive reimbursement recommendations. The median time from FDA approval to national HTA decision spans 1.54 years, with significant variation across countries. Key barriers to cost-effectiveness include reliance on single-arm trial designs, small study populations, and immature survival data. These findings underscore an urgent need for policy reforms and innovative access models to address the growing gap between scientific innovation and patient access.
Background: The Promise and Challenge of CAR T-Cell Therapies
Chimeric antigen receptor (CAR) T cells have fundamentally transformed the therapeutic landscape for patients with hematological malignancies, particularly those whose disease has relapsed or proven refractory to conventional chemotherapy. Since the first FDA approval in 2017, CAR T-cell therapies have demonstrated remarkable efficacy in conditions including acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and multiple myeloma. These autologous cellular therapies harness the patient’s own immune system, engineering T cells to recognize and eliminate cancer cells expressing specific surface antigens such as CD19 or BCMA.
However, the remarkable clinical potential of CAR T therapies is accompanied by substantial challenges. The manufacturing process for commercial autologous CAR T cells requires highly specialized facilities, rigorous quality control, and complex logistics involving cryopreservation and transportation. These factors contribute significantly to the high costs associated with these therapies, which can exceed $500,000 per treatment in some jurisdictions. Consequently, the widespread adoption of CAR T therapies has been limited, particularly in health systems with constrained resources or stringent cost-effectiveness thresholds.
In many countries, health technology assessment (HTA) bodies serve as critical gatekeepers for patient access to novel therapies. These independent agencies evaluate the clinical efficacy, safety, cost-effectiveness, and budget impact of new treatments to inform reimbursement decisions by public health systems or national insurance programs. Positive HTA recommendations typically enable patient access through government-funded healthcare programs, while negative recommendations may restrict or delay access entirely.
Study Design
Researchers conducted a comprehensive cross-sectional analysis of HTA evaluations for commercial CAR T therapies among the Group of 20 (G20) member countries, supplemented by three G20 invitees: Spain, Singapore, and Switzerland. The study examined all CAR T product-indication pairs with current FDA approval through August 1, 2025, encompassing a total of 18 distinct combinations across multiple approved indications.
The research team systematically reviewed HTA review documentation from 14 countries with publicly available assessment data. For each CAR T-indication pair, they ascertained the timing and rationale for HTA recommendations, categorizing decisions as positive (recommended for reimbursement) or negative (not recommended or not yet assessed). The analysis captured the interval between FDA regulatory approval and the corresponding HTA decision, as well as the evidentiary and economic arguments presented in HTA reports.
This methodology provides a standardized framework for comparing HTA decision-making across diverse healthcare systems with varying assessment criteria, threshold values, and processes. The inclusion of both G20 members and invitees enhances the comprehensiveness of the analysis, capturing regional variation in HTA practices.
Key Findings
The analysis revealed striking disparities in CAR T therapy access across the included jurisdictions. Among the 252 possible CAR T-indication pair assessments (18 product-indications across 14 countries), only 48% (122 pairs) currently receive positive reimbursement recommendations from public health systems. This finding indicates that even in high-income and upper middle-income countries with advanced healthcare infrastructure, fewer than half of available CAR T indications are accessible to patients through national reimbursement programs.
The temporal dynamics of HTA decision-making represent another significant finding. The median time from FDA approval to HTA decision was 1.54 years, with an interquartile range of 1.15 to 2.59 years. This delay means that patients in countries with slower HTA processes may wait over two years before CAR T therapies become available through public reimbursement, potentially missing the window for optimal treatment in cases of aggressive disease progression.
The study identified several recurring barriers to achieving favorable cost-effectiveness assessments. Single-arm trial designs emerged as a primary concern, as many CAR T approvals were based on pivotal trials lacking randomized controlled comparators. HTA bodies frequently cited the methodological limitations inherent in single-arm studies, including potential bias in patient selection and the absence of direct head-to-head comparisons with standard-of-care treatments. Small study populations in registration trials further compounded these concerns, reducing the statistical robustness of efficacy and safety estimates.
Immature follow-up data regarding long-term survival outcomes represented another critical barrier. Many CAR T trials reported initial response rates and progression-free survival data but lacked mature overall survival information at the time of HTA review. Quality of life assessments were similarly limited, with insufficient patient-reported outcome data to fully characterize the functional benefits and toxicities of CAR T therapies in real-world settings.
The economic arguments in HTA reports frequently centered on the substantial upfront costs of CAR T therapies relative to conventional treatments, compounded by uncertainty about long-term durability of response and the potential need for subsequent therapies. Some HTA bodies expressed concerns about budget impact at the health system level, particularly when considering multiple simultaneous CAR T approvals across different indications.
Subgroup analyses revealed considerable heterogeneity across countries and indications. Certain CAR T products with longer market experience and more mature follow-up data achieved higher rates of positive recommendations. Similarly, countries with higher cost-effectiveness thresholds or more flexible assessment frameworks demonstrated greater willingness to recommend CAR T reimbursement.
Expert Commentary
The findings of this study illuminate a fundamental tension in modern oncology: the rapid pace of scientific innovation often outstrips the capacity of health systems to evaluate, fund, and deliver these therapies equitably. CAR T-cell therapies exemplify this challenge, representing a genuine therapeutic advance validated by compelling clinical data, yet remaining inaccessible to substantial proportions of eligible patients globally.
The reliance on single-arm trial designs in CAR T development reflects the practical and ethical complexities of conducting randomized trials in life-threatening hematologic malignancies with limited treatment options. While this approach has enabled accelerated regulatory approvals, it has transferred the evidentiary burden to post-approval settings where HTA bodies must make consequential decisions with imperfect information. Innovative trial designs, including external control arms using real-world data, may partially address these limitations, though methodological controversies persist.
The 1.54-year median delay from FDA approval to HTA decision carries significant clinical implications. For patients with rapidly progressive malignancies, this interval may represent the difference between eligibility for CAR T therapy and disease progression beyond the window of benefit. Expedited assessment pathways for transformative therapies, as implemented in some jurisdictions, offer potential solutions but require careful balancing of efficiency against rigor.
The study’s limitations include the reliance on publicly available HTA documentation, which may not capture the full complexity of decision-making processes or confidential pricing arrangements. The cross-sectional design provides a snapshot of the access landscape as of August 2025 but cannot track temporal trends in HTA recommendations. Additionally, the analysis focuses on reimbursement decisions without fully capturing actual patient access, which may be further constrained by treatment center capacity, infrastructure requirements, and clinical eligibility criteria.
Future directions should include longitudinal monitoring of HTA recommendations as more mature follow-up data become available, comparative analysis of pricing and access strategies across jurisdictions, and evaluation of innovative financing models such as outcome-based agreements that link payment to clinical response.
Conclusion
This cross-sectional analysis documents substantial global disparities in access to CAR T-cell therapies, even among high-income and upper middle-income countries within the G20 network. With only 48% of approved indications receiving positive reimbursement recommendations and median assessment delays exceeding 1.5 years, many patients face significant barriers to accessing these potentially curative treatments.
The findings highlight the urgent need for both scientific and policy approaches to bridge the gap between CAR T innovation and equitable access. From the scientific perspective, improved trial designs with longer follow-up, comprehensive quality-of-life assessments, and head-to-head comparisons with standard therapies would strengthen the evidence base for HTA evaluations. From the policy perspective, accelerated assessment pathways, innovative financing mechanisms, and international collaboration on HTA methodologies could reduce delays and enhance consistency in reimbursement decisions.
As the CAR T therapeutic landscape continues to expand—with new targets, allogeneic products, and earlier-line indications in development—the imperative to address access disparities will only intensify. Ensuring that patients worldwide can benefit from these transformative therapies requires sustained engagement from researchers, clinicians, regulators, HTA bodies, payers, and policymakers alike.
Funding and Disclosures
This research was supported by institutional funding from the participating academic centers. The authors declare no conflicts of interest relevant to this study.
References
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2. FDA approves CAR T-cell therapy for relapsed or refractory ALL in adults. FDA News Release. 2024.
3. National Institute for Health and Care Excellence (NICE). CAR T-cell therapy appraisals: methodology and guidance. London: NICE; 2024.
4. World Health Organization. Health technology assessment of medical devices. Geneva: WHO; 2023.
