Point-of-care CAR T-cell therapy: toward broader access Open Access

In this issue of Blood Advances, Del Bufalo et al¹ present the results of a single-center phase 1/2 trial evaluating a point-of-care (POC)–manufactured CD19 chimeric antigen receptor (CAR) T-cell therapy in children and young adults with relapsed B-cell precursor acute lymphoblastic leukemia (B-ALL). This study is not only a proof of concept for decentralized CAR T-cell production in academic settings but also a compelling case for expanding access to this therapy to a new subgroup of patients: those with very high-risk (VHR) first relapse.

Currently, the only approved CAR T-cell product for pediatric B-ALL, tisagenlecleucel, is restricted to patients in second or subsequent relapses. In the clinical trial reported by Del Bufalo et al, children with VHR first relapse (who have poor outcomes with conventional therapy) were included and benefited from timely, locally produced CAR T-cell therapy. The reported 3-year event-free and overall survival rates (68% and 83%, respectively) were particularly striking and compared favorably to outcomes observed in pivotal trials of commercial products. Importantly, this was achieved with a good safety profile, with no cases of grade ≥3 cytokyne release syndrome or immune effector cell-associated neurotoxicity syndrome observed.¹ 

The manufacturing process, conducted on-site using a closed, automated system, was completed in 2 weeks, allowing for treatment within clinically actionable time frames. The authors emphasize the consistent manufacturing success across all patients, with robust cell expansion and transduction efficiencies. This operational feasibility, coupled with high response rates and durable remissions, positions POC CAR T-cell therapy as a practical and potentially scalable solution to overcome current limitations in access.

The study also reinforces the logistical and clinical advantages of local manufacturing. Patients with rapidly progressive disease often cannot wait through the weeks-long timelines associated with centralized manufacturing. By bringing production closer to the bedside, POC models offer a critical advantage for timely intervention.

What sets this study apart is its broader implication for the CAR T-cell field. It builds on previous academic initiatives such as the academic CAR T-cell program at Hospital Clínic de Barcelona, which similarly demonstrated that academic institutions can develop, manufacture, and deliver high-quality CAR T-cell products, with favorable clinical outcomes in different indications and at significantly reduced costs. Their CD19 CAR T-cell product, ARI-0001, obtained the approval, under the Hospital Exemption clause, by the Spanish Regulatory Medical Agency and the priority medicines designation by the European Medicines Agency.² These efforts underscore the viability of academic-driven innovation, especially for rare or neglected indications for which commercial interest is limited.

Encouragingly, the same CD19 CAR T-cell product used in the study reported by Del Bufalo et al will be evaluated in the upcoming IntReALL trial under a European pediatric oncology network. This multicenter initiative will test CD19 CAR T-cell therapy in VHR first relapse patients across multiple countries, using decentralized manufacturing hubs.³ If successful, it could serve as a model for the coordinated academic development of new CAR T-cell therapies targeting other pediatric indications, such as brain tumors, neuroblastoma, and other solid tumors or severe pediatric autoimmune diseases, many of which are not addressed by commercial pipelines.

The advantages are not limited to clinical access. POC manufacturing may significantly lower costs. For example, in Spain, ARI-0001 is reimbursed for less than one-third of the cost of commercially approved CAR T-cell products (€89 000 in a hospital exemption setting). India’s VELCART trial demonstrated a total cost of CAR T-cell therapy around $47 800, an order of magnitude lower than in high-income countries.⁴ 

However, as others have noted, POC manufacturing is not without challenges.⁵ Harmonization of protocols, quality oversight across sites, and sustainable funding remain essential for wider adoption.

In conclusion, the work by Del Bufalo et al provides important clinical and logistical evidence supporting the feasibility, safety, and impact of academic POC CAR T-cell models. Empowering academic centers to act as both developers and providers of advanced therapies may foster innovation, reduce costs, and, crucially, democratize access to life-saving treatments. This is essential to expand global access to CAR T-cell therapies, particularly for patients with rare diseases, including but not limited to pediatric populations, who are often left behind by conventional commercial development pathways.

Conflict-of-interest disclosure: S.R. reports personal fees and honoraria from Servier, Celgene/Bristol Myers Squibb, Kite/Gilead, and Amgen; consultancy fees, personal fees, and honoraria from Novartis; consultancy fees from Autolus; and honoraria and consultancy fees from OneChain Immunotherapeutics.