Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia

Author:

Moskop Amy1,Pommert Lauren23,Baggott Christina4,Prabhu Snehit5ORCID,Pacenta Holly L.6,Phillips Christine L.23,Rossoff Jenna7ORCID,Stefanski Heather E.8,Talano Julie-An1,Margossian Steve P.9,Verneris Michael R.10ORCID,Myers G. Doug11,Karras Nicole A.12,Brown Patrick A.13ORCID,Qayed Muna14,Hermiston Michelle L.15,Satwani Prakash16,Krupski Christa23,Keating Amy K.10,Wilcox Rachel11,Rabik Cara A.17,Fabrizio Vanessa A.10ORCID,Chinnabhandar Vasant18,Goksenin A. Yasemin15,Curran Kevin J.1920,Mackall Crystal L.21ORCID,Laetsch Theodore W.2223ORCID,Guest Erin M.11,Breese Erin H.23,Schultz Liora M.24

Affiliation:

1. 1Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, Medical College of Wisconsin, Children’s Wisconsin, Milwaukee, WI;

2. 2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH;

3. 3Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati OH;

4. 4Stanford University School of Medicine, Stanford, CA;

5. 5Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA;

6. 6Division of Hematology and Oncology, Cook Children's Medical Center, Fort Worth, TX;

7. 7Division of Hematology, Oncology and Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL;

8. 8Be the Match/National Marrow Donor Program, Minneapolis, MN;

9. 9Pediatric Hematology-Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard University, Boston, MA;

10. 10University of Colorado, Anschutz Medical Campus, Colorado Children’s Hospital, Aurora, CO;

11. 11Division of Hematology/Oncology/Blood and Marrow Transplant, Children’s Mercy Hospital, Kansas City, MO;

12. 12Department of Pediatrics, City of Hope National Medical Center, Duarte, CA;

13. 13Department of Oncology and Department of Pediatrics, Sidney Kimmel Cancer Center at Johns Hopkins, School of Medicine, Johns Hopkins University, Baltimore, MD;

14. 14Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA;

15. 15Department of Pediatrics, Benioff Children’s Hospital, University of California, San Francisco, San Francisco, CA;

16. 16Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, NY;

17. 17Division of Hematologic Malignancies I, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD;

18. 18Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN;

19. 19Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY;

20. 20Department of Pediatrics, Weill Cornell Medical College, New York, NY;

21. 21Division of Hematology and Oncology, Department of Pediatrics, Division of Stem Cell Transplantation and Cell Therapy, Department of Medicine, Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA;

22. 22Department of Pediatrics and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA;

23. 23Division of Oncology, Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA; and

24. 24Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA

Abstract

Abstract Infants with B-cell acute lymphoblastic leukemia (B-ALL) have poor outcomes because of chemotherapy resistance leading to high relapse rates. Tisagenlecleucel, a CD19-directed chimeric antigen receptor T-cell (CART) therapy, is US Food and Drug Administration approved for relapsed or refractory B-ALL in patients ≤25 years; however, the safety and efficacy of this therapy in young patients is largely unknown because children <3 years of age were excluded from licensing studies. We retrospectively evaluated data from the Pediatric Real-World CAR Consortium to examine outcomes of patients with infant B-ALL who received tisagenlecleucel between 2017 and 2020 (n = 14). Sixty-four percent of patients (n = 9) achieved minimal residual disease-negative remission after CART and 50% of patients remain in remission at last follow-up. All patients with high disease burden at time of CART infusion (>M1 marrow) were refractory to this therapy (n = 5). Overall, tisagenlecleucel was tolerable in this population, with only 3 patients experiencing ≥grade 3 cytokine release syndrome. No neurotoxicity was reported. This is the largest report of tisagenlecleucel use in infant B-ALL and shows that this therapy is safe and can be effective in this population. Incorporating this novel immunotherapy into the treatment of infant B-ALL offers a promising therapy for a highly aggressive leukemia.

Publisher

American Society of Hematology

Subject

Hematology

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