Kymriah (tisagenlecleucel-T)

P1, N=18, Not yet recruiting, Nathan Denlinger

Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).

T cell-redirecting therapies represent a central pillar in modern oncology, delivering high response rates across hematologic malignancies with expanding roles in earlier treatment settings. Future progress will depend on improving durability, optimizing sequencing, mitigating toxicity, and enhancing real-world deliverability through next-generation and multitarget platforms.

These findings suggest that SP dynamics may be linked to the early inflammatory response during CRS and support further investigation of the SP-NK1 receptor axis as a potential therapeutic target to modulate CD19 CAR-T-related toxicity.

Vignettes explored access to evidence-informed but not universally funded therapies: blinatumomab for low-risk relapse of B-cell acute lymphoblastic leukemia (B-ALL), larotrectinib for TRK-fused soft tissue sarcoma, PBT for unresectable head-and-neck sarcoma, and tisagenlecleucel for first relapse of B-ALL in a patient with Down syndrome. Access to evidence-informed cancer therapies for Canadian children remains variable. Universal funding, simplified approval processes, and the establishment of Canadian PBT centres to reduce travel burden, would ensure timely, equitable access to high-cost therapies.

P2, N=121, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Aug 2025 --> Oct 2027

In a single-institution retrospective cohort of pediatric and young adult patients with relapsed or refractory acute B-lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel between November 2023 and April 2025, two of 12 patients (17%) developed IEC-HS after CRS resolution, marked by recurrent fever, coagulopathy, hepatic dysfunction, cytopenias, and profound elevations in CXCL9, IL-18, and soluble C5b-9. Treatment with emapalumab led to rapid clinical and biomarker improvement. These findings support IEC-HS as an interferon-γ-driven syndrome and suggest targeted IFN-γ blockade as a potentially effective therapeutic strategy.

P=N/A, N=30, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

These findings highlight the importance of early leukapheresis, ideally before intensive treatments, to optimize T-cell yield, product quality, and therapeutic efficacy.

We conducted a single-center retrospective study of 69 patients treated with Tisagenlecleucel, to evaluate the prognostic impact of TP53 alterations (TP53Alt), including mutations and/or deletions...These findings identify TP53 alterations as a strong adverse prognostic factor in patients with r/r B-ALL treated with CAR-T therapy. Screening for TP53Alt may guide risk-adapted strategies, including early consolidation with hematopoietic stem cell transplantation or alternative therapies.

P4, N=75, Not yet recruiting, Universitair Ziekenhuis Gent

P3, N=331, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed