Kymriah (tisagenlecleucel-T)

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.

This study analyzed 24 R/R ALL patients receiving tisagenlecleucel after BT (Inotuzumab [n=10] vs. chemotherapy/steroids [n=14]). Overall, inotuzumab as BT effectively reduces tumor burden but attenuates CAR-T expansion without compromising survival outcomes. As high tumor burden is a dominant driver of relapse and toxicity, the net effect of inotuzumab may be favorable in selected patients.

Notably, tCAR-T exhibited superior antitumor activity compared to Kymriah, with enhanced cytokine release and improved target cell elimination. This innovative approach improves cancer treatment efficacy through enhanced binding avidity and modular targeting flexibility, demonstrating that tCAR-T can overcome limitations of conventional CAR-T therapy and highlighting its potential to improve therapeutic outcomes for cancer patients.

IEC-HS is a rare but potentially fatal complication. Our disproportionality analysis identifies significant reporting signals for tisa-cel and cilta-cel. The high absolute number of cases observed for products like axi-cel appears to reflect high utilization rather than a disproportionate risk, underscoring the necessity of using statistical signal detection methods when interpreting spontaneous reports.