The European CAR‐T map—Current status and future directions to improve access to CAR T‐cell therapy for hematologic malignancies

Abstract

Despite its great promise, implementation of CAR‐T therapy—a personalized, logistically complex, and expensive treatment—remains challenging, hampering patient access across and within countries. Since 2018, six products have been centrally approved in Europe (i.e., the European Economic Area; EU‐approved) for 15 hematologic malignancy indications. To better understand patient access to EU‐approved commercial CAR‐T therapy, we evaluated the current status in all 30 countries where EU‐approval is valid plus the UK, addressing economic, clinical, and organizational aspects, and identifying challenges and strategies for improvement. A two‐step approach was used, complementing data from marketing authorization holders (4/4 responded) with country‐specific insights from clinical experts obtained via an online survey (30/31 responded). In August 2024, 26% of the 31 countries had no CAR‐T products commercially available, 74% ≥ 1 product for non‐Hodgkin lymphoma and leukemia, and 16% ≥ 1 product for multiple myeloma. One‐time payment was the most used reimbursement method. Time to access varied significantly, with medians ranging from 0 (France/Germany) to 53 months (Slovakia). The median number of qualified CAR‐T centers per 10 million population per country was 5.0 (IQR: 3.0–6.1). In most countries, patient eligibility assessment was decentralized. Costs and logistical complexity were main factors restricting access in countries with and without commercially available products. Proposed solutions included cost reductions, improving reimbursement processes, and increasing healthcare resources. This study shows that patient access to commercial CAR‐T therapy in Europe remains limited. Its insights into this multi‐faceted problem can guide policy‐making, advocacy work, and research to make this transformative treatment accessible to more patients in need.

INTRODUCTION

Chimeric antigen receptor T‐cell (CAR‐T) therapy has emerged as a breakthrough in cancer treatment. For patients with relapsed or refractory (R/R) hematologic B‐cell malignancies, this innovative immunotherapy, utilizing genetically modified T‐cells expressing CARs to recognize and eliminate tumor cells, has led to significantly improved outcomes, with durable responses of ≥2 years and curative potential in subsets of patients. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ With many clinical trials ongoing, the number of CAR‐T products and indications are rapidly expanding, within and beyond the field of hemato‐oncology. ⁶ However, not all patients currently have access to this treatment, creating inequity between and even within countries. ³ , ⁷

In 2018, the first CAR‐T products were granted centralized marketing authorization by the European Commission (EC) (hereafter referred to as EU‐approved), based on recommendations of the European Medicines Agency (EMA): tisagenlecleucel (tisa‐cel) and axicabtagene ciloleucel (axi‐cel) for R/R B‐cell acute lymphoblastic leukemia (ALL) and/or large B‐cell lymphoma (LBCL). By April 2025, a total of six CAR‐T products had been EU‐approved for fifteen indications (Table 1, indications counted separately per product), primarily based on single‐arm phase II trial results: four CD19‐directed products (axi‐cel, tisa‐cel, lisocabtagene maraleucel [liso‐cel], and brexucabtagene autoleucel [brexu‐cel]) for R/R ALL and/or R/R B‐cell non‐Hodgkin lymphoma (NHL) subtypes (LBCL, mantle cell lymphoma [MCL], and/or follicular lymphoma [FL]) and two products targeting the B‐cell maturation antigen (idecabtagene vicleucel [ide‐cel] and ciltacabtagene autoleucel [cilta‐cel]) for R/R multiple myeloma (MM). ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ The EU‐approval is valid in the European Economic Area (EEA), including all European Union (EU) member states (N = 27), Iceland, Liechtenstein, and Norway. Consequently, eligible patients in these countries could potentially be treated with commercial CAR‐T therapy in daily clinical practice (i.e., outside clinical trials). Yet, implementation in clinical practice is challenging, as it is a logistically complex, personalized, and expensive treatment for several reasons, as illustrated in Table 2. To implement CAR‐T therapy, it is important to secure reimbursement that preferably covers not only the CAR‐T product but also the associated healthcare costs. Adequate infrastructure and sufficient resources are also essential, for instance, qualified centers to provide CAR‐T therapy, effective referral and patient eligibility assessment pathways, CAR‐T manufacturing capabilities, including apheresis services, as currently only autologous products are EU‐approved, and healthcare resources for CAR‐T infusion and management of acute and long‐term CAR‐T toxicities. ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ , ⁴⁴ , ⁴⁵ , ⁴⁶

Table 1.

EU‐approved indications and products by August 2024 with respective approval dates categorized per disease subgroup, including an update to April 2025 indicated with an “a” in superscript. ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹

Indication (N = 14 → 15a)	Product (N = 6)	Date of EU‐approval
B‐cell acute lymphoblastic leukemia (N  = 2)
Pediatric and young adult patients up to and including the age of 25 with R/R ALL that is refractory or in relapse post‐transplant or in second or later relapse. 25	Tisagenlecleucel	23‐08‐2018
Adult patients 26 years of age and older with R/R ALL. 27	Brexucabtagene autoleucel	02‐09‐2022
B‐cell non‐hodgkin lymphoma (N  = 8 → 9 a )
Adult patients with R/R DLBCL or PMBCL after two or more lines of systemic therapy. 24	Axicabtagene ciloleucel	23‐08‐2018
Adult patients with R/R DLBCL after two or more lines of systemic therapy. 25	Tisagenlecleucel	23‐08‐2018
Adult patients with R/R MCL after two or more lines of systemic therapy, including a Bruton's tyrosine kinase inhibitor. 27	Brexucabtagene autoleucel	14‐12‐2020
Adult patients with R/R DLBCL, PMBCL, or FL3B after two or more lines of systemic therapy. 26	Lisocabtagene maraleucel	04‐04‐2022
Adult patients with R/R FL after two or more lines of systemic therapy. 25	Tisagenlecleucel	29‐04‐2022
Adult patients with R/R FL after two or more lines of systemic therapy. 26 ,a	Lisocabtagene maraleucela	12‐03‐2025a
Adult patients with R/R FL after three or more lines of systemic therapy. 24	Axicabtagene ciloleucel	21‐06‐2022
Adult patients with DLBCL or HGBCL that relapses within 12 months from completion of, or is refractory to, first‐line chemoimmunotherapy. 24	Axicabtagene ciloleucel	14‐10‐2022
Adult patients with DLBCL, HGBCL, PMBCL, and FL3B, who relapsed within 12 months from completion of, or are refractory to, first‐line chemoimmunotherapy. 26	Lisocabtagene maraleucel	28‐04‐2023
Multiple myeloma (N  = 4)
Adult patients with R/R MM who have received at least three prior therapies, including an IMid, a PI, and an anti‐CD38 antibody, and have demonstrated disease progression on the last therapy. 28	Idecabtagene vicleucel	18‐08‐2021
Adult patients with R/R MM who have received at least three prior therapies, including an IMid, a PI, and an anti‐CD38 antibody, and have demonstrated disease progression on the last therapy. 29	Ciltacabtagene autoleucel	25‐05‐2022
Adult patients with R/R MM who have received at least two prior therapies, including an IMid, a PI, and an anti‐CD38 antibody, and have demonstrated disease progression on the last therapy. 28	Idecabtagene vicleucel	19‐03‐2024
Adult patients with R/R MM, who have received at least one prior therapy, including an IMid and a PI, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. 29	Ciltacabtagene autoleucel	19‐04‐2024

Abbreviations: ALL, B‐cell acute lymphoblastic leukemia; DLBCL, diffuse large B‐cell lymphoma; FL, follicular lymphoma; FL3B, follicular lymphoma grade 3B; HGBCL, high‐grade B‐cell lymphoma; IMid, immunomodulatory agent; MCL, mantle cell lymphoma; MM, multiple myeloma; PI, proteasome inhibitor; PMBCL, primary mediastinal B‐cell lymphoma; R/R, relapsed or refractory.

^aBetween August 2024 and April 2025, one additional indication has been EU‐approved (lisocabtagene maraleucel for adult patients with R/R FL after two or more lines of systemic therapy), resulting in a total of six CAR‐T products being EU‐approved for fifteen indications (indications counted separately per CAR‐T product) by April 2025. Notably, in case ≥1 CAR‐T product has been EU‐approved for the same indication, this is counted as a separate indication per product. For example, two CAR‐T products (tisagenlecleucel and lisocabtagene maraleucel) have been EU‐approved for adult patients with R/R FL after two or more lines of systemic therapy, which is counted as two indications.

*Large B‐cell lymphoma includes DLBCL and HGBCL, and depending on the CAR‐T product reimbursed, may also include PMBCL and/or FL3B.

Table 2.

Implementation of CAR‐T therapy in clinical practice—characteristics of EU‐approved commercial CAR‐T products and how these may impact patient access in Europe.

	Characteristics of EU‐approved commercial CAR‐T products	Examples of potential impact on patient access
	List prices often exceed €300,000/$400,000 per CAR‐T product. 30 , 32 , 33	Acquisition costs can be substantial and may raise affordability concerns and complicate reimbursement, especially in case of limited long‐term follow‐up and lack of studies head‐to‐head comparing effectiveness with the current standard of care. 30 , 31 , 32 , 33
	As per EU‐approval requirements, centers need to be qualified by the CAR‐T manufacturers (i.e., marketing authorization holders [MAHs]) to provide CAR‐T therapy. 40 , 41	The process to become a CAR‐T center can vary by country and may involve additional stakeholders, including health authorities and/or professional societies. 40 , 41
	Although typically only a single infusion of this “living drug” is needed, the treatment trajectory consists of several phases starting with referral and patient eligibility assessment.	Referral and patient eligibility assessment can vary across countries and impact access; for example, it can be centralized in regional networks or national tumorboards applying uniform eligibility criteria and promoting equal and timely patient access. 32 , 42 , 43 , 44 , 45
	After screening, apheresis and CAR‐T manufacturing follow.	Labor‐intensive, as currently only autologous CAR‐T therapies are EU‐approved; each patient receives their own custom‐manufactured CAR T‐cells. During the manufacturing period, patients may need bridging therapy to control the disease. This might result in CAR‐T ineligibility, for example, in case of rapidly progressive disease that cannot be effectively bridged. 42
	To monitor and adequately treat CAR‐T toxicities, such as cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, hematotoxicity, and infections, CAR‐T infusion often involves inpatient admission, patients staying close to the CAR‐T center during the first month and follow‐up for up to 15 years post‐infusion. 3 , 40 , 46	CAR T‐therapy, including toxicity management and supportive care such as bridging/lymphodepleting therapy, antimicrobial prophylaxis/treatment, transfusions, growth factors, and intravenous immunoglobulins, places a high burden on healthcare resources (e.g., requiring trained personnel, apheresis services, and inpatient and ICU beds) and involves significant additional healthcare costs.

Hence, access to CAR‐T therapy is a multifaceted challenge involving different stakeholders, including patients, informal caregivers, healthcare professionals, CAR‐T manufacturers, and policymakers, encompassing economic, clinical, and organizational aspects such as costs and reimbursement, adequate education, training and awareness among patients and healthcare providers (e.g., understanding of patient eligibility and timely referral), availability of healthcare resources, logistics, including qualification procedures, number and geographical spread of CAR‐T centers, (inter)national regulations, and CAR‐T manufacturing capacity. ⁷ , ⁴⁷ , ⁴⁸ , ⁴⁹ , ⁵⁰ Possible solutions to improve patient access include off‐the‐shelf and point‐of‐care CAR‐T products and outpatient treatment, which becomes more feasible with improving toxicity management and innovative monitoring strategies. ¹ , ³⁰ , ⁵¹ , ⁵² , ⁵³

Some studies previously analyzed access to EU‐approved CAR‐T therapies for select products, indications, and European countries, primarily major countries such as France, Germany, Italy, Spain, and the United Kingdom (UK) (i.e., the EU5). ³² , ³⁴ , ³⁶ , ³⁷ , ⁴⁵ However, while essential to identify next steps, little is known about the current status across all EEA countries and the actual size of the problem of unequal access.

With the aim to better understand patient access to EU‐approved commercial CAR‐T therapy for hematologic malignancies and to outline directions for improvement, this study evaluates access to the six EU‐approved products and provides a comprehensive overview of the current status in all countries where the EU‐approval is valid. It examines economic aspects, such as reimbursed products and indications and time to access in each country, which contribute toward determining the actual size of the problem. To further analyze patient access, it also assesses clinical and organizational aspects, including patient eligibility assessment and CAR‐T center qualification, identifies barriers, and explores possible solutions. The study was conducted in the context of T2EVOLVE, an alliance of academic and industry leaders working together to accelerate development and increase access to CAR‐T therapies. ⁵⁴ By mapping the current landscape, we provide key insights to support advocacy work, evidence‐based policy making, and future research aiming to make this treatment available to more patients.

METHODS

Study design and geographical scope

This cross‐sectional study focused on all countries for which the EC issues its marketing authorization (i.e., the EEA, N = 30) and the UK, as a former EU member state, and hence included 31 countries.

Data collection

We used a two‐step approach and collected data from (1) marketing authorization holders (MAHs) and (2) leading clinical experts in this field (i.e., physicians, preferably involved in implementation of CAR‐T therapy in their country), as these were considered valuable information sources that could complement each other.

We asked all four manufacturers of the six EU‐approved products to provide data regarding access to their CAR‐T products, including information on the reimbursement status (along with reimbursement dates) per country, product and indication, and the number of qualified CAR‐T centers per country and product.

To further evaluate economic, clinical, and organizational aspects of patient access and identify challenges and possible solutions to improve access, CAR‐T and HTA experts within the T2EVOLVE consortium developed an online survey to obtain country‐specific insights from leading clinical experts (one expert per country). The survey, comprising mainly multiple‐choice and some open questions, evaluated accessibility of the CAR‐T products (N = 6) and indications (N = 11) that were EU‐approved prior to January 1, 2023, in daily clinical practice (Table 1). It was available in English and disseminated between April and October 2023. All questions were mandatory, except for the question “other remarks”. Clinical experts were explicitly asked to answer the survey regarding access to commercial CAR‐T therapy and the situation in their country (i.e., from a national perspective), not just their hospital. All respondents provided informed consent online to participate in the study.

Finally, to ensure up‐to‐date information at the same time point for all six CAR‐T products for the analyses, we requested the MAHs to update the provided data to the status in August 2024 (N = 14 EU‐approved indications, Table 1). As the CAR‐T field is rapidly evolving, we also requested a final update on reimbursed indications at manuscript submission (April 2025) to include the latest developments and demonstrate the dynamic nature.

Assessment of country‐specific insights on patient access to commercial CAR‐T therapy from leading clinical experts

The first part of the survey covered demographics, provided a description of the EU‐approved CAR‐T products and indications prior to January 1, 2023, and a multiple‐choice question to indicate which EU‐approved CAR‐T products were commercially available in each respondent's country to treat patients with a hematologic malignancy. Depending on the answer to this question, specific follow‐up questions appeared. All respondents were asked to estimate per indication the number of patients they expected could be treated with CAR‐T therapy per year, if centers should treat a minimum number of patients with CAR‐T therapy per year to be qualified to provide it (if yes, number), and to specify factors currently restricting and possible solutions to improve access to commercial CAR‐T products.

In case a respondent indicated that no CAR‐T products were commercially available, they were additionally asked if they expected it would become commercially available (if yes, when; if no, reason).

Respondents who indicated that ≥1 CAR‐T products were commercially available received additional questions per selected product to specify whether the product was reimbursed and for which indications. Subsequently, for each selected indication, questions appeared to specify the reimbursement date and method (one‐time payment, pay‐for‐performance, etc.), whether additional costs such as leukapheresis, hospital stay, management of adverse events, and follow‐up were reimbursed, and whether the use of the specific CAR‐T product for the specific indication was incorporated into national guidelines as part of standard of care (SoC). Regardless of the CAR‐T products selected, respondents were asked to specify the decision‐making process to decide which patients are eligible for commercially available CAR‐T therapy (centralized, decentralized, etc.) and which centers should be qualified to provide it, the type and number of centers providing commercial CAR‐T therapy, and which hematologic indications they expect will probably be treated with commercial CAR‐T therapy in the near future (within five years), including the specific product and estimated number of patients per year.

Data analysis

Descriptive statistics were used for analyses, which included frequencies, proportions, means, medians, and (interquartile) ranges where appropriate.

The total number of products and respective indications being reimbursed per country and categorized into three disease subgroups, ALL, NHL, and MM, were visualized with heatmaps to highlight geographical differences across Europe.

Time to access was defined as, per EU‐approved CAR‐T product and respective indication(s), the period (in months) from approval to reimbursement or access via an early access program and was calculated per country. If no information or only the year of reimbursement was provided, the information was considered missing; if only the day was missing, it was replaced by the first day of the reported month. A combined bar chart, including error bars, and dot plot was created to visualize time to access.

For each country, the number of qualified CAR‐T centers represents the maximum number of centers qualified by a MAH. To calculate the ratios of qualified CAR‐T centers and CAR‐T eligible patients per population, we used total population estimates as of July 1, 2024 per country retrieved from the 2024 revision of the United Nations World Population Prospects. ⁵⁵

To account for missing data, complete‐case sensitivity analyses were conducted where appropriate.

For open questions (i.e., the questions about possible solutions for improving access and the decision‐making process to qualify CAR‐T centers), similar responses were categorized into themes; these themes, with frequencies, were reported.

Factors restricting access and possible solutions were analyzed separately for countries with and without commercially available CAR‐T products to evaluate any possible subgroup‐specific challenges and solutions. A bar chart was created to visualize the distribution of factors restricting access.

Statistical analyses were performed using R software (Version 4.4.3).

RESULTS

All MAHs responded and provided the requested information either in part or in full, 4/4 MAHs provided information on reimbursement status per country, product, and indication, with 3/4 MAHs also providing the reimbursement dates, and 3/4 MAHs additionally provided the number of qualified CAR‐T centers per country.

In total, 30 clinical experts, representing all countries, except for Liechtenstein, responded. Of these clinical experts, 67% (n = 20/30) worked at a CAR‐T center and most experts specifically focused on lymphoma (73%; n = 22), followed by MM (43%; n = 13) and leukemia (33%; n = 10), with 11 experts (37%) selecting multiple hematologic malignancies. Additionally, three clinical experts (10%) indicated to not specifically focus on one of these hematologic malignancies. The median time to response from initial survey dissemination (April 2023) was 22 days (IQR: 1–89 days).

In the following paragraphs, we present our findings regarding economic, clinical, and organizational aspects of access to commercial CAR‐T therapy, followed by the challenges and possible solutions to improve access.

Economic aspects of access

We first examined, per country, whether CAR‐T products were reimbursed and for which indications. As presented in Table 1, a total of six CAR‐T products were EU‐approved for fourteen indications by August 2024 (ALL: N = 2, NHL: N = 8, MM: N = 4). Indications were counted separately per CAR‐T product, to consider the availability of multiple products for the same indication. Figure 1 shows the total number of products and respective indications reimbursed by August 2024 for each country (N = 31) overall and stratified per disease subgroup. In 26% of the countries (n = 8), including Bulgaria, Cyprus, Estonia, Iceland, Latvia, Liechtenstein, Lithuania, and Malta, no EU‐approved CAR‐T products were reimbursed. Clinical experts from Luxembourg and Iceland indicated that they send their patients abroad to receive CAR‐T therapy (at the time of filling in the survey, no CAR‐T products were yet reimbursed in Luxembourg, but the clinical expert had already indicated that this might happen in the near future). In the other countries (74%; n = 23), at least a CAR‐T product for ALL and NHL was reimbursed and 16% (n = 5) had ≥1 CAR‐T product reimbursed to treat patients with MM. Only in Germany and Austria (6%) were all six CAR‐T products reimbursed for all 14 indications. Further zooming in on the specific indications reimbursed by August 2024, presented in Table 3, CAR‐T therapy for R/R MM had the lowest accessibility, especially the two most recently EU‐approved indications as ≥second‐ and ≥third‐line treatment, being reimbursed only in Germany and Austria (6%). Accessibility to CAR‐T products for adult patients with R/R FL (29%) and ALL (36%) ranked second and third lowest and only in six of these countries patients with R/R FL could receive CAR‐T therapy as third‐line treatment. CAR‐T products for R/R LBCL (second line) and MCL (≥third line) were accessible in approximately half of the countries (45% and 48%, respectively). Best accessible were CAR‐T products for R/R LBCL in ≥third line (71%) and ALL for patients <26 years (71%).

Figure 1.

Access to EU‐approved commercial CAR‐T products in Europe defined as the total number of products and respective indications reimbursed by August 2024 in each country (N = 31) overall (A) and stratified per disease subgroup (B, C, and D).

Table 3.

Access^a to commercial CAR‐T products for the EU‐approved indications in 31 countries in Europe by August 2024, including an update to April 2025.

Abbreviations: ALL, B‐cell acute lymphoblastic leukemia; FL, follicular lymphoma; LBCL, large B‐cell lymphoma; MCL, mantle cell lymphoma; MM, multiple myeloma; R/R relapsed or refractory.

^a Access defined as CAR‐T products and respective indications being reimbursed (in green) and not reimbursed (in blue) in a country. In case multiple CAR‐T products are EU‐approved for a similar indication (i.e., for R/R LBCL and R/R MM), the number of CAR‐T products reimbursed is also indicated for that specific indication. The update to April 2025, in case of any developments between August 2024 and April 2025, is reflected by arrows and cells with a blue/green checkered pattern or multiple X's. Arrows were used to indicate changes in the total CAR‐T products and indications reimbursed, in case an additional CAR‐T product was reimbursed by April 2025 for an indication for which already a CAR‐T product was reimbursed by August 2024, and in case a CAR‐T product was no longer reimbursed in April 2025 for an indication for which multiple CAR‐T products were reimbursed by August 2024 (this is the case for Germany). Cells with a blue/green checkered pattern indicate that ≥1 CAR‐T products were reimbursed by April 2025 for an indication for which no CAR‐T products were yet reimbursed by August 2024. A cell with multiple X's indicates that CAR‐T products are no longer reimbursed in April 2025 for an indication for which only one CAR‐T product was reimbursed by August 2024 (this is the case for Germany). As shown, in Germany, Czech Republic, Spain, Greece, the United Kingdom, Sweden, Norway, Poland, the Netherlands, and Denmark, the number of reimbursed CAR‐T products and indications changed between August 2024 and April 2025.

^b LBCL includes diffuse large B‐cell lymphoma, high‐grade B‐cell lymphoma, and depending on the CAR‐T product reimbursed/reimbursement specifications may also include primary mediastinal B‐cell lymphoma and/or follicular lymphoma grade 3B.

^c Between August 2024 and April 2025, one additional CAR‐T product has been EU‐approved for adult patients with R/R FL in ≥3^rd line. However, for this CAR‐T product an update for the indication R/R FL in ≥3^rd line was not provided; hence, it is unkown whether this CAR‐T product had already been reimbursed for this indication in any of the countries by April 2025.

As it is a dynamic field, Table 3 also provides an update to April 2025 to reflect the latest developments. In April 2025, 26% of the countries (n = 8) still had no reimbursed EU‐approved CAR‐T products. Among the countries with ≥1 CAR‐T product reimbursed (n = 23), 39% (n = 9) experienced an increase in the number of reimbursed products and respective indications between August 2024 and April 2025, whereas one country (4%) experienced a decrease.

For the EU‐approved CAR‐T products and respective indications reimbursed by August 2024, time to access differed substantially between and within countries, as shown in Figure 2 and Supporting Information S1: Table 1. The median time to access in the 23 countries with ≥1 EU‐approved CAR‐T products reimbursed was 16.5 months. Germany and France had almost immediate access and Austria ranked third, with median times of 0 and 4.5 months, respectively. Conversely, the median time to access was the longest in Slovakia, Hungary, Ireland, and Romania, with 53.4, 52.3, 41.4, and 41.3 months, respectively. Within‐country differences (min–max ranges) were the largest in Luxembourg, Norway, the Netherlands, and Slovakia.

Figure 2.

Time to access ^a calculated from EU‐approval date in months and number of indications reimbursed per country by August 2024. ^aTime to access was defined as, per EU‐approved CAR‐T product and respective indication(s), the period (in months) from EU‐approval to reimbursement or access via an early access program. As no CAR‐T products were commercially available in Bulgaria, Cyprus, Estonia, Iceland, Latvia, Liechtenstein, Lithuania, and Malta, time to access could not be calculated for these countries. Above each bar, the median time to access in months, calculated from the EU‐approval date, per country is provided, with, between brackets, the number of reimbursed indications per country by August 2024 and in superscript the number of indications for which a reimbursement date was available and that subsequently could be used to calculate time to access (e.g., in Hungary and Austria, 2 and 14 indications were reimbursed by August 2024, respectively, and for 1 and 9 indication(s), respectively, the reimbursement date(s) was/were available and used to calculate time to access in Hungary and Austria). For nine countries, Hungary (missing dates/total number of reimbursed indications; n = 1/2 [50%]), Ireland (n = 2/3 [67%]), Portugal (n = 1/4 [25%]), Italy (n = 3/10 [30%]), Sweden (n = 1/5 [20%]), Czech Republic (n = 3/8 [38%]), Austria (n = 5/14 [36%]), France (n = 3/10 [30%]), and Germany (n = 3/14 [21%]), reimbursement dates for one or more indications were missing; hence, median time to access and the minimum and maximum time could be an under‐ or overestimation. The error bars indicate the minimum and maximum time to access per country. *Median time to access in the 23 countries with ≥1 EU‐approved CAR‐T product reimbursed (mean; min–max): 16.5 months (21.3; 0–62.3).

According to the clinical experts from countries with ≥1 CAR‐T products reimbursed (n = 22), one‐time payment was the most frequently used reimbursement method. In 82% (n = 18/22) of the countries, additional healthcare costs such as leukapheresis, hospital stay, adverse event management, and follow‐up were reimbursed for one or more indications. In case additional costs were reimbursed, these were most often fully reimbursed.

Clinical aspects of access

Based on responses from countries with ≥1 CAR‐T products commercially available, CAR‐T products were often also incorporated into national guidelines as SoC when reimbursed.

The decision‐making process to decide which patients are eligible for commercially available CAR‐T therapy is more often decentralized (59%; n = 13/22, i.e., decision made at the CAR‐T treating center) than centralized (41%; n = 9/22).

Survey respondents' estimates of the number of patients who could be treated with CAR‐T therapy per year, per indication and country, provided in Supporting Information S1: Table 2, quantify the population in need. The median estimated CAR‐T eligible population per one million population in Europe per year for the 11 EU‐approved indications prior to January 1, 2023, was 23.6 (IQR: 18.7–34.8), based on complete data from 11 countries.

Organizational aspects of access

Organizational aspects of access include CAR‐T center qualification. The number of qualified CAR‐T centers and rate per 10 million population per country in August 2024 are provided in Table 4 and ranged from 1 to 15 per 10 million population, with a median of 5 centers per country (IQR: 3–6). Mainly Eastern European, but also some Western European countries, such as Norway and the UK, rated below this median. The highest rate per 10 million population was observed in Luxembourg (notably, only one CAR‐T center was qualified, but its population of only 0.7 million explains this high estimate per 10 million population), followed by Czech Republic, Belgium, Spain, and Austria, while Hungary had the lowest rate, followed by Romania, Norway, Slovakia, and Poland.

Table 4.

Number of qualified CAR‐T centers by at least one of the four marketing authorization holders and as rate per 10 million population per country in August 2024.

Country	Estimated number of qualified CAR‐T centers per 10 million populationa	Reported number of qualified CAR‐T centers	Population as of July 1, 2024 in millions 55
Luxembourgb	14.9	1	0.7
Czech Republic	7.5	8	10.7
Belgium	6.8	8	11.7
Spain	6.7	32	47.9
Austriab	6.6	6	9.1
Italy	6.2	37	59.3
Greece	6.0	6	10.0
Sweden	5.7	6	10.6
Finlandb	5.3	3	5.6
Germany	5.3	45	84.6
France	5.3	35	66.5
Denmarkb	5.0	3	6.0
Sloveniab	4.7	1	2.1
The Netherlands	4.4	8	18.2
Portugal	3.8	4	10.4
Irelandb	3.8	2	5.3
The United Kingdom	3.3	23	69.1
Croatiab	2.6	1	3.9
Poland	2.3	9	38.5
Slovakiab	1.8	1	5.5
Norwayb	1.8	1	5.6
Romania	1.1	2	19.0
Hungaryb	1.0	1	9.7
Bulgaria	0.0	0	6.8
Cyprus	0.0	0	1.4
Estonia	0.0	0	1.4
Iceland	0.0	0	0.4
Latvia	0.0	0	1.9
Liechtenstein	0.0	0	0.04
Lithuania	0.0	0	2.9
Malta	0.0	0	0.5

^a Median (mean; IQR) number of qualified CAR‐T centers per 10 million population for all 23 countries in Europe with one or more CAR‐T products reimbursed: 5.0 (4.9; 3.0–6.1).

^b In countries with one or more CAR‐T products reimbursed and a population of less than 10 million, the estimated number of qualified CAR‐T centers per 10 million population can be higher than the reported number of qualified CAR‐T centers.

Regarding the type of centers and the decision‐making process to qualify centers to provide CAR‐T therapy, variances across Europe were identified based on responses from countries with ≥1 CAR‐T product commercially available (n = 22). In 55% of these countries, centers were required to be transplant/JACIE‐accredited (JACIE: Joint Accreditation Committee, ISCT [International Society for Cellular Therapy], and EBMT [European Society for Blood and Marrow Transplantation]). In addition, national and/or regional health authorities, professional societies, and/or health insurance companies were involved in 55%, 23%, and 9% of the countries, respectively. Among the types of centers providing commercially available CAR‐T therapy, academic medical centers (university hospitals) were included in all countries (n = 22). Additionally, in some countries, public centers (community hospitals; n = 4 countries), non‐profit private centers (n = 3), for‐profit private centers (n = 2), and/or a national center for pediatric oncology (n = 1) also provided CAR‐T therapy.

In total, 61% of the respondents indicated that centers should treat a minimum number of patients with CAR‐T therapy per year to be qualified; the median minimum number reported was 12 patients (min–max: 2–30).

Challenges and possible solutions to improve access

Among clinical experts from the eight countries without commercially available CAR‐T products, four did expect it to become commercially available to treat hematologic malignancies in their country, possibly within 5 years, and three did not anticipate this, primarily because it was deemed too expensive (n = 3) and also too complex to implement in the national healthcare system (n = 1).

Figure 3 depicts the factors restricting access according to survey respondents, stratified by countries with and without commercially available CAR‐T products. The most commonly reported restricting factors were costs (67%) and logistical complexity in terms of healthcare resources (47%; such as limited number of hospital beds (including intensive care unit [ICU] capacity), availability of (timely) apheresis services, trained staff, and/or qualified CAR‐T centers). In countries without access, both these factors were most frequently mentioned (71%). Conversely, in countries with access, costs were more frequently mentioned than logistical complexity (65% vs. 39%) and also referral was often mentioned as a restricting factor (43%), followed by production slot availability (26%) and logistical complexity in terms of geographical spread of CAR‐T centers and associated burden due to travel distance (17%). Other factors included small country, no JACIE‐accredited transplantation centers, and competition with bispecific antibodies.

Figure 3.

Factors restricting access according to survey respondents stratified for countries with and without commercially available CAR‐T products ^a .

^aThese data are only based on survey responses (N = 30; Liechtenstein missing). Respondents could select multiple options; the answer options “logistical complexity in terms of geographical spread of CAR‐T treating centers” and “Availability of production slots of MAHs” were only available in case respondents had indicated that at least one CAR‐T product was commercially available in their country.

^bOther reasons include no reimbursement, ongoing discussions, small country, no JACIE‐accredited transplantation centers, access is not restricted, and competition with bispecific antibodies.

Possible solutions to improve access provided by the survey respondents were categorized; reducing costs and improving cost‐effectiveness and reimbursement processes (e.g., innovative reimbursement strategies, long‐term follow‐up, and/or academic CAR‐T production) was most frequently mentioned both by respondents from countries with and without access to commercial CAR‐T products. In countries with access, this was closely followed by increasing healthcare resources (e.g., number of qualified CAR‐T centers, trained staff, hospital beds [including ICU capacity], and/or apheresis services) and next ranked increasing awareness of CAR‐T eligible patients (e.g., through central multidisciplinary team meetings and/or more information for referring centers), faster and improved production processes (e.g., point‐of‐care production and/or more flexibility in production slots), and collaboration with MAHs to establish national market access. Other proposed solutions included simplifying center qualification processes and outpatient treatment. In countries without access, solutions other than reducing costs and improving cost‐effectiveness/reimbursement processes were far less frequently reported and included increasing healthcare resources, simplifying center qualification processes, increasing awareness of CAR‐T eligible patients, and collaboration with CAR‐T centers abroad.

DISCUSSION

CAR‐T therapy significantly improves outcomes for patients with R/R hematologic malignancies and is increasingly recommended in European and national clinical guidelines, but as its implementation remains complex, currently, not all patients in Europe have access. ⁵⁶ , ⁵⁷

This study showed that, in August 2024, in 26% of the 31 European countries evaluated (the 30 EEA countries plus the UK), mainly in Eastern Europe, patients had no access to EU‐approved CAR‐T products outside clinical trials. Moreover, in three of these countries, commercial availability was not expected either, primarily because it was deemed too expensive. Access becomes even more restricted across specific EU‐approved indications. Most strikingly, only five countries (16%) had CAR‐T products for R/R MM commercially available. Access to commercial products for adults with R/R FL (29%), ALL (36%), and LBCL (in second line; 45%), but also for earlier approved indications such as MCL (48%), is also lagging behind. More encouragingly, for R/R LBCL (in ≥third line) and ALL (for patients <26 years), 22 countries (71%) had commercial CAR‐T products available. Time to access after EU‐approval significantly varied across and within countries. When excluding countries without access, the median time to access was 17 months and ranged between >4 years (Slovakia/Hungary) and <6–0 months post‐EU‐approval (Germany/France/Austria/the UK). Notably, also, some Western European countries faced considerable delays. Among countries with access, the median number of qualified CAR‐T centers per 10 million population was five and patient eligibility assessment was decentralized in most countries. Both in countries with and without commercially available products, costs and logistical complexity in terms of healthcare resources were identified as main factors restricting access and reducing costs, and improving cost‐effectiveness and reimbursement processes was the most commonly reported solution. In countries with access, referral was also frequently mentioned as a restricting factor and increasing healthcare resources as a strategy to improve access.

As patients in countries without commercially available CAR‐T products also have limited access to innovative therapies, including CAR‐T therapy, through clinical trials, this presents a significant problem. ⁵⁸ As reported here and previously, some of these countries, including Latvia, Luxembourg, Iceland, and Malta, can send patients abroad to receive CAR‐T treatment. ³² , ⁵¹ However, to what extent cross‐border care represents a sustainable solution to improve patient access should be further explored, especially considering the expanding indications and that challenges such as costs, timely referral, and manufacturing capacity may persist. Additionally, it requires well‐structured cross‐border collaboration and that patients are able to travel abroad for a certain period, which may be logistically, physically, and/or emotionally burdensome. ³² , ⁵⁹

Differences in commercial availability across indications may partially be explained by more recent approval of the first CAR‐T product for R/R MM compared to R/R ALL and NHL (in 2021 vs. 2018). Additionally, the clinical added value is not uniform across CAR‐T products and indications, as effectiveness (specifically curative potential), level of evidence (e.g., follow‐up period, single‐arm or randomized trial), and alternative treatment options (comparative (cost‐)effectiveness) differ and might influence access and reimbursement decisions. As previously reported, for the first two EU‐approved products and indications (R/R ALL and LBCL), performance‐based risk‐sharing arrangements (PBRSAs), such as outcomes‐based reimbursement and coverage with evidence development, were effectively used in Belgium, France, Germany, Italy, Spain, and the UK, to facilitate early access to promising high‐cost single‐infusion CAR‐T therapies despite considerable uncertainty about long‐term outcomes. ³⁰ , ³² , ³⁴ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁴ Additionally, such PBRSAs can generate further evidence, potentially addressing uncertainties, validating clinical trial results in real‐world populations, and supporting outcome prediction (e.g., optimizing patient selection). ³⁴ , ³⁸ , ⁴² However, implementation of PBRSAs can be challenging; it requires good governance processes and collecting evidence is costly, as the administrative burden and associated monitoring, evaluation, and negotiation costs can be significant. ³⁴ , ³⁸ , ⁶⁰ Our study showed that one‐time payment was the most frequently used reimbursement method for CAR‐T products (actual prices paid can still be influenced by price negotiations and discounts, but due to the confidentiality of these processes, this information was not collected). Future studies should examine to what extent PBRSAs or alternative reimbursement and pricing methods could improve CAR‐T access. Notably, CAR‐T treatment also involves substantial healthcare costs besides acquisition costs, also after one year post‐infusion. ³⁰ , ⁶¹ According to our respondents, these additional healthcare costs (e.g., for leukapheresis, hospital admission, adverse event management, and follow‐up) were reimbursed in most countries. The actual total costs of CAR‐T therapy, however, often remain unknown, due to confidential price negotiations and/or the influence of PBRSAs. Also, outcomes of cost‐effectiveness analyses seem to vary considerably, which could be attributed to several factors such as limited (long‐term) evidence especially, lack of direct comparisons, use of noncontemporaneous comparators, and difficulties in determining exact treatment costs. ⁶² , ⁶³ Recommendations to mitigate these shortcomings have been studied elsewhere and include collection of real‐world data, independent publicly available indirect treatment comparisons, comparisons with modern clinically relevant treatments, and increased supply chain pricing transparency. ⁶² , ⁶³

Importantly, as of January 12, 2025, the EU joint clinical assessment as part of the new EU HTA regulation applies to novel cancer medicines and advanced therapy medicinal products (ATMPs). ⁶⁴ This could help improve the availability of CAR‐T therapies and possibly expedite time to access, as relative clinical effectiveness is evaluated at the European level. In addition, relevant clinical outcomes such as survival and quality of life, as well as procedures to address uncertainty and assess evidence from early‐phase clinical trials, will become more standardized across Europe. Nevertheless, reimbursement decisions will still be made at the national level, although cross‐country collaborations, such as joint health technology assessments and price negotiations, are being explored (e.g., the Beneluxa Initiative). ⁶⁴ , ⁶⁵ , ⁶⁶

Similar to our results, another study assessing access to 12 novel cancer treatments in Europe found time to market, defined as time from EU‐approval to first sales, was fastest in Germany, the UK, and Austria. ⁶⁷ Like in France, early access programs can significantly shorten time to access. Hence, we recommend that future studies further evaluate the exact design and use of early access programs across Europe and their potential to provide rapid access to novel therapies such as CAR‐T therapy. Wide within‐country variances in time to access observed in our study could be caused by earlier and more recently EU‐approved indications being simultaneously reimbursed, like in Luxembourg, or indication‐specific reimbursement challenges, like in Norway and the Netherlands, where CD19‐directed CAR‐T therapy was reimbursed faster for pediatric/young adults with R/R ALL than adults with R/R LBCL. This may be in part caused by differing sizes of the population qualifying for these therapies, which is important for the budget impact, a measure often used to inform reimbursement decisions. As also demonstrated in our study, the estimated number of CAR‐T eligible patients for R/R ALL (<26 years) is substantially lower than for R/R LBCL. The provided estimates of CAR‐T eligible patients per indication per year can be used to calculate the impact of no or restricted access and the budget impact of CAR‐T therapy in each country. However, these numbers could be underestimated, as clinical experts might have taken current availability and capacity into account. For instance, for France, Italy, and Spain, the estimates for R/R DLBCL are lower than previously reported numbers. ⁴⁵ Additionally, missing data probably resulted in an underestimation of the calculated total estimated CAR‐T eligible populations per indication and per country, and for four countries, data were completely absent, as survey respondents did not provide any estimates. Hence, further investigation is needed.

Commercial availability, however, does not guarantee patient access. Previous studies reported that 31%–83% of patients with the EU‐approved indication did not receive CAR‐T therapy, highlighting the significant unmet need despite the availability of CAR‐T therapy in a country. ⁴² , ⁴⁵ , ⁶⁸ Other factors may hamper patient access initially or during the treatment trajectory, such as referral, capacity to manufacture and deliver CAR‐T cells, patient characteristics, including ethnicity and socioeconomic status, and disease characteristics, such as rapidly progressive disease, which cannot be effectively bridged during CAR‐T manufacturing. ⁴² , ⁴⁷ , ⁴⁸ , ⁴⁹ , ⁶⁸ , ⁶⁹ , ⁷⁰ , ⁷¹ , ⁷² As shown in our study, in case reimbursed, CAR‐T products are often incorporated into national guidelines as SoC. However, additional criteria for patients to be eligible may apply. ³² , ⁴² , ⁴⁴ , ⁴⁵ , ⁶⁸ For example, in Italy, an age limit for CAR‐T therapy for R/R LBCL applies (tisa‐cel/axi‐cel: 75/70 years). ⁴⁴ Additionally, decentralized patient eligibility assessment and access procedures may complicate patient access and contribute to within‐country disparities. For example, in Italy, Spain, and Germany, access procedures can be further decentralized to the regional, local, or patient level. ³⁴ , ⁴⁴ , ⁴⁵ Furthermore, timelines can significantly impact access. For instance, Chen et al. showed that a wait time reduction of 2 months increased the number of eligible patients with DLBCL truly receiving CAR‐T therapy (tisa‐cel) by minimally 10.7% and resulted in increased survival gains of 3.3% per infused patient. ⁷³

Regarding the number of qualified CAR‐T centers in August 2024, compared to previously reported numbers from 2020 for Belgium, France, Germany, Italy, Spain, the United Kingdom, and Norway, our study showed an expected significant increase in these countries, except for Norway, and as anticipated, a center was qualified in Hungary. ³² , ⁴⁵ Additionally, our findings can be compared with the CAR‐T center density reported for the top 25 countries in 2022 by Passweg et al., who found a strong correlation of CAR‐T center density with CAR‐T treatment rates and a correlation, though less strong, with gross national income. ⁷⁴ For European countries, the minimum number of CAR‐T centers per 10 million population increased from 0.5 to 1, and an increase of ≥1 center per 10 million population was observed for 9/21 countries (Hungary, Luxembourg, and Slovakia were not included, as no data for 2022 were reported), possibly indicating increased CAR‐T therapy utilization in these countries between 2022 and 2024. However, besides these numbers, geographical spread should also be considered. In countries with limited or unequally distributed CAR‐T centers, travel distance and out‐of‐region referrals (e.g., in countries with decentralized access procedures like Italy) could become additional barriers. ⁴⁴ , ⁴⁵ , ⁴⁷ To better understand variations in the application of CAR‐T therapy across countries, future studies could explore the ratio of CAR‐T treatment centers per number of hospitals in a country, how correlations between economic factors (e.g., gross national income and healthcare/pharmaceutical expenditure) with CAR‐T center density and treatment rates evolve over time, and whether economic factors correlate with the number of CAR‐T indications reimbursed, reimbursement of specific indications (e.g., ALL, NHL, and MM), or time to access.

The factors restricting access and possible solutions identified here align with previous studies. Since the introduction of CAR‐T therapy, concerns about access have been raised and concrete solutions include innovative reimbursement strategies (e.g., outcomes‐based reimbursement), outpatient administration, which could, among others, reduce resource use, and off‐the‐shelf (e.g., in vivo or allogeneic CAR‐T therapy) and point‐of‐care products. ¹ , ⁷ , ³⁰ , ³² , ³⁴ , ³⁵ , ³⁷ , ⁴⁴ , ⁴⁵ , ⁴⁷ , ⁵¹ , ⁵² , ⁵³ , ⁶² , ⁷⁵ For instance, the academically developed point‐of‐care CAR‐T products in Spain significantly reduced manufacturing time and, with a price of €89,270, substantially improved affordability. ⁵¹ Also worth mentioning is the hospital exemption (HE) clause, which applies specifically to ATMPs (ATMP Regulation article 28 amends the EU general pharmaceutical legislation) and offers an exception to the compulsory centralized marketing authorization for ATMPs under certain conditions. ⁷⁶ , ⁷⁷ EU member states can use this clause nationally to improve patient access to ATMPs and address unmet needs, fostering ATMP development and possibly bridging to centralized marketing authorization. For example, via the HE framework, the academic point‐of‐care CAR‐T product ARI‐0001 and allogeneic CAR‐T product (ALLO_GD2‐CART01) were developed and provided to patients aged >25 years with R/R ALL in Spain and patients with R/R neuroblastoma who had no alternative treatment options in Italy, respectively. ⁵¹ , ⁷⁷ , ⁷⁸ , ⁷⁹ However, as a recent EC study demonstrated, HE implementation, including the application procedure (e.g., timelines and data requirements), its use, and restrictions, substantially differs across member states. ⁷⁷

Ongoing initiatives to ensure equitable patient access across Europe include the reform of the EU pharmaceutical legislation, which, for example, involves rewarding MAHs with prolonged data protection if they launch their product in all member states where the authorization is valid or address unmet needs, and changes to improve the HE application. ⁷⁷ , ⁷⁹ , ⁸⁰ , ⁸¹ Additionally, EMA offers support for ATMP development via the PRIME (Priority Medicines) scheme and a pilot specifically for academic and non‐profit developers, and since January 2025, offers non‐profit entities a fee waiver for scientific advice. ⁷⁷ , ⁸²

As this study focused on the availability of EU‐approved products as SoC, the use of other CAR‐T products, including off‐the‐shelf and point‐of‐care products, within or outside clinical trials via HE, was not evaluated, but would be an interesting area for future research.

While this study focused on European countries, the identified access barriers are not unique to this region. Costs, infrastructure, and governmental support are recognized as main barriers hampering access to CAR‐T therapy globally. ⁸³ To varying extents, access is also heterogenous across other regions, including the United States (US), Latin America, Africa, and Asia. ³ , ⁴⁷ , ⁷⁰ , ⁷⁵ , ⁸⁴ , ⁸⁵ In several regions, countries are developing locally manufactured CAR‐T products as a strategy to reduce costs and enhance affordability, for example, in the United States, India, Brazil, South Africa, and Spain (discussed above). ⁵¹ , ⁸⁴ , ⁸⁵ , ⁸⁶ , ⁸⁷ Additionally, sociodemographic factors may influence CAR‐T access, which has, for instance, been reported as an important barrier in the United States, alongside other barriers, including costs, logistics, referral, and manufacturing. ⁴⁷ , ⁷⁰ , ⁷⁵ For example, black patients, patients with a lower income, and patients who had considerable travel time to the nearest CAR‐T center were less likely to receive CAR‐T therapy outside clinical trials in the United States. ⁷² , ⁸⁸ Furthermore, studies showed an unequal geographic distribution of clinical trial sites across the United States, and racial and ethnic minorities such as black and Hispanic patients are often underrepresented in CAR‐T clinical trials. ⁷¹ , ⁸⁸ , ⁸⁹ The financial toxicity associated with CAR‐T therapy could create an additional access barrier, especially for patients with a lower socioeconomic status. For example, no or limited insurance coverage, including high deductibles and co‐pays, can substantially increase out‐of‐pocket expenses. Also, travel time and costs, including temporary housing expenses, can become considerable (e.g., in the United States, < 4% of healthcare centers provide CAR‐T therapy). ⁶² , ⁷¹ , ⁷⁵

Limitations of our study include the ±6‐month survey period; initial responses could therefore be outdated when last responses were obtained, as the CAR‐T field is rapidly evolving. However, most responses were collected within the first three months. Also, specific follow‐up questions, on the reimbursement method, reimbursement of additional costs, and incorporation into national guidelines, per CAR‐T product and indication, only appeared if the clinical expert indicated that it was reimbursed. Therefore, this information was missing in case clinical experts' responses on reimbursement status, provided in 2023, differed from the updated MAHs provided for August 2024. Notably, time to access could be under‐ or overestimated, as reimbursement dates for one or more indications were missing in nine countries. As detailed information on the specific centers qualified per MAH was not available, we could not sum the qualified CAR‐T centers without precluding double counting and took the maximum number qualified by a MAH per country, which could be an underestimation. While the survey was disseminated among leading clinical experts, reliance on responses of one expert per country could have introduced bias. For example, although respondents were explicitly asked to provide country‐specific insights from a national perspective, the information provided could potentially reflect the experience of one center or region and may not be representative of the entire country. Additionally, while the survey covered different aspects of access, its results only reflect the views of clinical experts. We partially accounted for these limitations by complementing respondents' insights with information from MAHs and vice versa. Further research including the perspectives of various experts, such as patient, regulatory, and HTA experts, and triangulation with independent data sources, such as reports from official institutions (e.g., health authorities, professional societies, regulatory agencies, and HTA bodies), is needed to broaden our understanding of patient access to CAR‐T therapy.

This is the first cross‐sectional study evaluating the complex issues of access to all six EU‐approved commercial CAR‐T therapies for hematologic malignancies across all countries where the EU‐approval is valid plus the UK. Its findings show that implementation of this expensive and logistically complex personalized treatment remains challenging, hampering patient access, highlight key challenges, and propose solutions, differentiating between countries with and without access. The presented data were gathered through collaboration with both MAHs and clinical experts, underscoring the importance of a multi‐stakeholder approach to improve access. By addressing economic, clinical, and organizational aspects, this study provides a comprehensive overview of the current landscape, enabling comparisons across 31 countries, and offers valuable quantitative insights that can inform policymakers, support advocacy work, and guide future research aimed at improving patient access to innovative therapies such as CAR‐T therapy. Moving forward, continuous monitoring of access improvements–leveraging the European network being established and the systematic methodology applied in this study–will be essential to identify best practices, successful strategies, and future directions. As its application is expanding, it is imperative to address the existing access barriers and facilitate broader implementation of CAR‐T therapy for those indications in which there is substantial proven benefit for patients.

AUTHOR CONTRIBUTIONS

Elise R. A. Pennings: Conceptualization; methodology; project administration; resources; investigation; data curation; formal analysis; writing—original draft; writing—review and editing. Frederick W. Thielen: Conceptualization; methodology; resources; data curation; formal analysis; writing—original draft; writing—review and editing. Florence Broussais: Resources; data curation; formal analysis; writing—review and editing. Julio Delgado: Resources; writing—review and editing. Ulrich Jaeger: Resources; writing—review and editing. Carmen Sanges: Project administration; resources; writing—review and editing. Yolanda Cabrerizo: Project administration; resources; writing—review and editing. Lutgart Roux‐Opstaele: Project administration; resources; writing—review and editing. Caroline Dreuillet: Project administration; resources; writing—review and editing. Eglys Gonzalez‐Marcano: Project administration; resources; writing—review and editing. Olga Millán: Project administration; resources; writing—review and editing. Barbara Huber: Project administration; resources; writing—review and editing. Solène Clavreul: Resources; writing—review and editing. Natacha Bolaños: Resources; writing—review and editing. Samantha Nier: Resources; writing—review and editing. Jana Mihályová: Resources; writing—review and editing. Roman Hájek: Resources; writing—review and editing. Michaela Horňáková: Resources; writing—review and editing. Robin Doeswijk: Resources; data curation; formal analysis; writing—review and editing. Catherine Thieblemont: Resources; data curation; formal analysis; writing—review and editing. Michael Hudecek: Resources; writing—review and editing. Carin A. Uyl‐de Groot: Conceptualization; methodology; resources; data curation; formal analysis; writing—original draft; writing—review and editing. Marie José Kersten: Conceptualization; methodology; resources; investigation; data curation; formal analysis; writing—original draft; writing—review and editing.

CONFLICT OF INTEREST STATEMENT

FWT has been involved in research (partly) funded by Celgene B.V., Canadian Agency for Drugs and Technologies in Health (CADTH), the National Institute for Health and Care Excellence (NICE), the Dutch Healthcare Institute (ZIN), the Dutch Ministry of Health, Welfare and Sport (VWS), and the Swiss Federal Office of Public Health (FOPH), and the European Hematology Association (EHA). In 2020, he consulted AstraZeneca on a reimbursement dossier for a treatment and disease indication unrelated to this project. He was invited speaker for Boehringer Ingelheim in 2023. UJ received honoraria from/served on advisory boards for BMS, Gilead, Janssen, Novartis, and Miltenyi; consultancy: BMS and Gilead. BH is a member of advisory boards for Janssen and Roche. JM has had a consultant or advisory relationship with Janssen, AbbVie, BMS, and Novartis, and has received honoraria from Janssen, AbbVie, BMS, and Novartis. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda; is a member of advisory boards for BMS, Takeda, Amgen, Oncopeptides, Sanofi, Janssen, and GSK; and has received support for attending meetings and/or travel from Amgen, Celgene, Takeda, and Janssen. CT discloses a direct financial relationship (honoraria) with Janssen, Roche, AbbVie, Novartis, BMS, Incyte, and BeiGene. MHu is listed as a co‐inventor on patent applications and granted patents related to CAR technologies and CAR‐T cell therapy that have been filed by the Fred Hutchinson Cancer Research Center, Seattle, WA, and the University of Wuerzburg, Wuerzburg, Germany, that have been, in part, licensed to industry. MHu is a co‐founder and equity owner of T‐CURX GmbH, Wuerzburg, Germany. MHu further declares speaker honoraria from Novartis, Kite/Gilead, BMS/Celgene, and Janssen. CAUG reports research funding from Boehringer lngelheim, Janssen Cilag, Genzyme, Astellas, Sanofi, Roche, AstraZeneca, Amgen, Gilead, Merck, Novartis, Bayer, National Institutes of Health (NIH, Harvard), the European Hematology Association (EHA), and ASCERTAIN (grant EU) (all payments to the institution). MJK received honoraria from and has a consulting/advisory role for BMS/Celgene, Kite, a Gilead Company, Miltenyi Biotec, Galapagos, Novartis, Adicet Bio, Mustang Bio, Janssen, and Roche, research funding from Kite, a Gilead Company, and travel support from AbbVie, Roche, and BMS (all to institution). ERAP, FB, JD, CS, YC, LRO, CD, EGM, OM, SC, NB, SN, MHo, and RD declare no conflicts of interest.

ETHICS STATEMENT

Not applicable.

FUNDING

This research was funded by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 945 393, T2EVOLVE; this Joint Undertaking receives support from the European Union's Horizon 2020 Research and Innovation Program, the European Federation of Pharmaceutical Industries and Associations (EFPIA), and the European Hematology Association (EHA). This article reflects the views of the authors and not of the funders of the project.

Supporting information

Access to CAR‐T in Europe_Supplementary appendix.pdf.

DATA AVAILABILITY STATEMENT

The data presented in this study are available from the corresponding author upon reasonable request.