Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia

Amy Moskop¹, Lauren Pommert^{2

3}, Christina Baggott⁴, Snehit Prabhu⁵, Holly L Pacenta⁶, Christine L Phillips^{2

3}, Jenna Rossoff⁷, Heather E Stefanski⁸, Julie-An Talano¹, Steve P Margossian⁹, Michael R Verneris¹⁰, G Doug Myers¹¹, Nicole A Karras¹², Patrick A Brown¹³, Muna Qayed¹⁴, Michelle L Hermiston¹⁵, Prakash Satwani¹⁶, Christa Krupski^{2

3}, Amy K Keating¹⁰, Rachel Wilcox¹¹, Cara A Rabik¹⁷, Vanessa A Fabrizio¹⁰, Vasant Chinnabhandar¹⁸, A Yasemin Goksenin¹⁵, Kevin J Curran^{19

20}, Crystal L Mackall²¹, Theodore W Laetsch^{22

23}, Erin M Guest¹¹, Erin H Breese^{2

3}, Liora M Schultz²⁴

Affiliations

¹ Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI.
² Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH.
³ Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati OH.
⁴ Stanford University School of Medicine, Stanford, CA.
⁵ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA.
⁶ Division of Hematology and Oncology, Cook Children's Medical Center, Fort Worth, TX.
⁷ Division of Hematology, Oncology and Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
⁸ Be the Match/National Marrow Donor Program, Minneapolis, MN.
⁹ Pediatric Hematology-Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard University, Boston, MA.
¹⁰ University of Colorado, Anschutz Medical Campus, Colorado Children's Hospital, Aurora, CO.
¹¹ Division of Hematology/Oncology/Blood and Marrow Transplant, Children's Mercy Hospital, Kansas City, MO.
¹² Department of Pediatrics, City of Hope National Medical Center, Duarte, CA.
¹³ Department of Oncology and Department of Pediatrics, Sidney Kimmel Cancer Center at Johns Hopkins, School of Medicine, Johns Hopkins University, Baltimore, MD.
¹⁴ Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, GA.
¹⁵ Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA.
¹⁶ Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, NY.
¹⁷ Division of Hematologic Malignancies I, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
¹⁸ Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN.
¹⁹ Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY.
²⁰ Department of Pediatrics, Weill Cornell Medical College, New York, NY.
²¹ Division 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 Department of Pediatrics and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA.
²³ Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA; and.
²⁴ Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.

PMID: 35580324
PMCID: PMC9327536
DOI: 10.1182/bloodadvances.2021006393

Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia

Amy Moskop et al. Blood Adv. 2022.

. 2022 Jul 26;6(14):4251-4255.

doi: 10.1182/bloodadvances.2021006393.

Authors

Affiliations

¹ Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI.
² Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH.
³ Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati OH.
⁴ Stanford University School of Medicine, Stanford, CA.
⁵ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA.
⁶ Division of Hematology and Oncology, Cook Children's Medical Center, Fort Worth, TX.
⁷ Division of Hematology, Oncology and Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
⁸ Be the Match/National Marrow Donor Program, Minneapolis, MN.
⁹ Pediatric Hematology-Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard University, Boston, MA.
¹⁰ University of Colorado, Anschutz Medical Campus, Colorado Children's Hospital, Aurora, CO.
¹¹ Division of Hematology/Oncology/Blood and Marrow Transplant, Children's Mercy Hospital, Kansas City, MO.
¹² Department of Pediatrics, City of Hope National Medical Center, Duarte, CA.
¹³ Department of Oncology and Department of Pediatrics, Sidney Kimmel Cancer Center at Johns Hopkins, School of Medicine, Johns Hopkins University, Baltimore, MD.
¹⁴ Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, GA.
¹⁵ Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA.
¹⁶ Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, NY.
¹⁷ Division of Hematologic Malignancies I, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
¹⁸ Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN.
¹⁹ Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY.
²⁰ Department of Pediatrics, Weill Cornell Medical College, New York, NY.
²¹ Division 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 Department of Pediatrics and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA.
²³ Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA; and.
²⁴ Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.

PMID: 35580324
PMCID: PMC9327536
DOI: 10.1182/bloodadvances.2021006393

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.

Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

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Figures

**Figure 1.**
Swimmer plot illustrating the clinical course of patients with infant B-ALL following CART infusion.

See this image and copyright information in PMC

References

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Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia

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Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia

Authors

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