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

Authors

null

Jonathan Bender

Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Jonathan Bender , Sudarshawn Damodharan , Amy Moskop , Keri Toner , Anant Vatsayan , Christian Capitini , Christina Baggott , Deborah E. Schiff , Emmanuel Katsanis , Sunil S. Raikar , Julie-An M. Talano , Liora M. Schultz , Lauren Pommert

Organizations

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, Department of Pediatrics, Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, School of Medicine & Public Health, University of Wisconsin; UW Carbone Cancer Center, Madison, WI, Medical College of Wisconsin, Milwaukee, WI, Division of Oncology, Division of Blood and Marrow Transplantation, Children's National Hospital; Department of Pediatrics, George Washington School of Medicine and Health Sciences, Washington, DC, Division of Blood and Marrow Transplantation, Children's National Health System; Department of Pediatrics, George Washington School of Medicine and Health Sciences, Washington, DC, University of Wisconsin School of Medicine and Public Health, Madison, WI, Stanford University School of Medicine, Stanford, CA, Division of Hematology-Oncology, Rady Children's Hospital; Department of Pediatrics, University of California San Diego, San Diego, CA, Department of Pediatrics, University of Arizona; Departments of Immunobiology, Medicine, and Pathology, University of Arizona; University of Arizona Cancer Center, Tucson, AZ, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, Department of Pediatrics, Division of Hematology/Oncology/Blood and Marrow Transplantation; Medical College of Wisconsin and Children’s Wisconsin, Milwaukee, WI, Stanford University School of Medicine, Palo Alto, CA, Cincinnati Children’s Hospital Medical Center, Cancer and Blood Diseases Institute; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH

Research Funding

No funding received
None.

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.

Prior # Therapies, median (range)4 (1-8)
Prior HSCT3/10 (30%)
Best Overall Response of Complete Response6/10 (60%)
 B-Lymphoblastic4/5 (80%)
 Burkitt0/1 (0%)
 Diffuse Large B-Cell1/2 (50%)
 Primary Mediastinal B-Cell1/2 (50%)
Disease Status at Last Assessment Alive, No Disease 7 (70%) | Alive, With Disease 1 (10%) | Deceased 2 (20%)
Cytokine Release Syndrome: Any Grade | Grade ≥37 (70%) | 1 (10%)
Neurotoxicity: Any Grade | Grade ≥32 (20%) | 1 (10%)

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Pediatric Oncology

Track

Pediatric Oncology

Sub Track

Leukemia/Lymphoma

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 10031)

DOI

10.1200/JCO.2023.41.16_suppl.10031

Abstract #

10031

Poster Bd #

337

Abstract Disclosures