Kymriah (tisagenlecleucel-T)

P=N/A, N=500, Recruiting, Novartis Pharmaceuticals | N=179 --> 500

P3, N=200, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Apr 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

P3, N=109, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1, N=20, Recruiting, Stanford University | Trial completion date: Nov 2025 --> Jul 2026 | Trial primary completion date: Nov 2025 --> Jul 2026

P2, N=30, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2026 --> Jul 2027 | Trial primary completion date: Jul 2026 --> Jul 2027

P2, N=396, Recruiting, SWOG Cancer Research Network | Trial completion date: Dec 2029 --> Jun 2030 | Trial primary completion date: Dec 2025 --> Jun 2030

P=N/A, N=30, Not yet recruiting, Novartis Pharmaceuticals

CD19-targeted CAR T cells, such as tisagenlecleucel, have demonstrated high rates of complete remission and long-lasting responses in clinical trials...Despite these innovations, further research is needed to refine manufacturing processes, reduce costs, and improve long-term outcomes. This review emphasizes the transformative potential of CAR-T therapy for pediatric B-ALL and discusses critical challenges and future directions in the field.

By contrast, CARpos T cells obtained from infusion products in long-term responders are enriched in the CD38-CD73-Tim-3-HLA-DR+ phenotype, characterized by a decreased ability to produce adenosine, memory-like transcriptomic characteristics, and leveraging of mitochondrial metabolism and oxidative phosphorylation. Our study reveals that the CD38-CD73-Tim-3-HLA-DR+ phenotype contributes to long-term remission in patients with BCP-ALL who receive tisagenlecleucel.

P1/2, N=30, Suspended, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 --> Dec 2026 | Recruiting --> Suspended | Trial primary completion date: Dec 2025 --> Sep 2026

Altogether, these findings suggest administering ibrutinib before leukapheresis may modify T-cell characteristics in the collected material, thereby improving final CAR T-cell product quality and clinical outcomes for patients with R/R LBLC treated with tisagenlecleucel. This trial was registered at www.clinicaltrials.gov as #NCT03876028.

To investigate this clinical issue, 106 patients treated with CAR-T cell therapy using either tisagenlecleucel, lisocabtagene maraleucel or axicabtagene ciloleucel for r/r DLBCL at our institution were retrospectively analyzed. Multivariate analysis revealed that CD5 expression was unfavorably associated with PFS and OS. Together, these data suggest that CD5 expression has a negative impact on outcomes after CAR-T cell therapy.