Real-world use of tisagenlecleucel in children and young adults with relapsed or refractory B-cell lymphomas.

Abstract

10031 Background: Survival for pediatric B-cell lymphomas (BCL) exceeds 90% with modern regimens, however outcomes remain poor for patients with relapsed or refractory (R/R) disease. Tisagenlecleucel is a CD19-directed CAR T-cell therapy (CART) that is FDA approved for adults with R/R BCL. No data exists for use of tisagenlecleucel in R/R pediatric BCL. Methods: We surveyed 48 sites in the Pediatric Real-World CAR Consortium to retrospectively describe use and outcomes of tisagenlecleucel for pediatric patients with R/R BCL. This cohort included 10 patients from 7 centers aged ≤25 years who were infused between 2019-2022 and were ≥3 months from CART. We aimed to describe response rates, as determined by each institution based on positron emission tomography, bone marrow evaluation, and/or cerebrospinal fluid (CSF) studies, along with toxicity and outcomes in this population. Results: Ten patients received CART with a median age at infusion of 19 (range, 7-24) years. Five patients had B-lymphoblastic lymphoma (B-LLy), 2 had primary mediastinal BCL, and 1 each had Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and post-transplant lymphoproliferative disorder related DLBCL. Five patients had primary refractory disease, and 5 were in ≥2nd relapse. Three had received prior hematopoietic stem cell transplant (HSCT). Two had CSF involvement, and 1 had central nervous system parenchymal disease at time of infusion. CART was well tolerated with 1 patient experiencing grade 3 cytokine release syndrome and 2 patients experiencing neurotoxicity (grade 2 n = 1, grade 3 n = 1), both of whom had CSF involvement at time of CART infusion. Best overall response was complete response (CR) for 6, partial response (PR) for 2, and refractory disease for 2. Two patients, both with B-LLy, underwent allogeneic HSCT while in CART-mediated CR with B-cell aplasia. Both patients with PR (1 DLBCL, 1 Burkitt) subsequently relapsed with CD19-negative disease; the patient with DLBCL subsequently achieved CR with salvage immuno-chemotherapy and HSCT. All 6 CR patients remain in remission at a median time to follow-up of 31 (range, 14-47) months. Conclusions: This multicenter case series of CD19-directed CART for R/R pediatric BCL suggests that tisagenlecleucel may be safe and active in this population with all CR patients currently in sustained remission. Larger studies are needed to understand how best to incorporate CART into treatment for R/R pediatric BCL. [Table: see text]