EClinicalMedicine (Nov 2023)
Tisagenlecleucel utilisation and outcomes across refractory, first relapse and multiply relapsed B-cell acute lymphoblastic leukemia: a retrospective analysis of real-world patternsResearch in context
- Valentin Barsan,
- Yimei Li,
- Snehit Prabhu,
- Christina Baggott,
- Khanh Nguyen,
- Holly Pacenta,
- Christine L. Phillips,
- Jenna Rossoff,
- Heather Stefanski,
- Julie-An Talano,
- Amy Moskop,
- Susanne Baumeister,
- Michael R. Verneris,
- Gary Douglas Myers,
- Nicole A. Karras,
- Stacy Cooper,
- Muna Qayed,
- Michelle Hermiston,
- Prakash Satwani,
- Christa Krupski,
- Amy Keating,
- Vanessa Fabrizio,
- Vasant Chinnabhandar,
- Michael Kunicki,
- Kevin J. Curran,
- Crystal L. Mackall,
- Theodore W. Laetsch,
- Liora M. Schultz
Affiliations
- Valentin Barsan
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA
- Yimei Li
- Department of Pediatrics, Children's Hospital of Philadelphia/University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA; Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
- Snehit Prabhu
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA
- Christina Baggott
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA
- Khanh Nguyen
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA
- Holly Pacenta
- Cook Children’s Hospital, 1500 Cooper St 5th Floor, Fort Worth, TX 76104, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center/Children’s Health, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA
- Christine L. Phillips
- Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA; Cincinnati Children’s Hospital Medical Center, Cancer and Blood Disease Institute, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA
- Jenna Rossoff
- Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611, USA
- Heather Stefanski
- Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Ave S AO-102, Minneapolis, MN 55454, USA
- Julie-An Talano
- Department of Pediatric Hematology Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA
- Amy Moskop
- Department of Pediatric Hematology Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA
- Susanne Baumeister
- Dana Farber/Boston Children’s Hospital, 450 Brookline Avenue Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA
- Michael R. Verneris
- University of Colorado, Anschutz Medical Campus, Colorado Children’s Hospital, 13123 East 16th Avenue, Aurora, CO 80045, USA
- Gary Douglas Myers
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA; Department of Pediatrics, Children's Hospital of Philadelphia/University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA; Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA; Cook Children’s Hospital, 1500 Cooper St 5th Floor, Fort Worth, TX 76104, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center/Children’s Health, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA; Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA; Cincinnati Children’s Hospital Medical Center, Cancer and Blood Disease Institute, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA; Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611, USA; Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Ave S AO-102, Minneapolis, MN 55454, USA; Department of Pediatric Hematology Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA; Dana Farber/Boston Children’s Hospital, 450 Brookline Avenue Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA; University of Colorado, Anschutz Medical Campus, Colorado Children’s Hospital, 13123 East 16th Avenue, Aurora, CO 80045, USA; Children’s Mercy Hospital, 2401 Gillham Rd, Kansas City, MO 64108, USA; Department of Pediatrics, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, USA; Department of Oncology, Sidney Kimmel Cancer Center at John Hopkins School of Medicine, Baltimore, MD, USA; Emory University and Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA; University of California San Francisco Benioff Children’s Hospital, 1975 4th St., San Francisco, CA 94158, USA; Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford Cancer Institute, 265 Campus Drive, Stanford, CA 94305, USA; Division of Blood and Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Room H0101, Stanford, CA 94305-5623, USA
- Nicole A. Karras
- Department of Pediatrics, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, USA
- Stacy Cooper
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA; Department of Pediatrics, Children's Hospital of Philadelphia/University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA; Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA; Cook Children’s Hospital, 1500 Cooper St 5th Floor, Fort Worth, TX 76104, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center/Children’s Health, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA; Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA; Cincinnati Children’s Hospital Medical Center, Cancer and Blood Disease Institute, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA; Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611, USA; Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Ave S AO-102, Minneapolis, MN 55454, USA; Department of Pediatric Hematology Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA; Dana Farber/Boston Children’s Hospital, 450 Brookline Avenue Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA; University of Colorado, Anschutz Medical Campus, Colorado Children’s Hospital, 13123 East 16th Avenue, Aurora, CO 80045, USA; Children’s Mercy Hospital, 2401 Gillham Rd, Kansas City, MO 64108, USA; Department of Pediatrics, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, USA; Department of Oncology, Sidney Kimmel Cancer Center at John Hopkins School of Medicine, Baltimore, MD, USA; Emory University and Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA; University of California San Francisco Benioff Children’s Hospital, 1975 4th St., San Francisco, CA 94158, USA; Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA; Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford Cancer Institute, 265 Campus Drive, Stanford, CA 94305, USA; Division of Blood and Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Room H0101, Stanford, CA 94305-5623, USA
- Muna Qayed
- Emory University and Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA
- Michelle Hermiston
- University of California San Francisco Benioff Children’s Hospital, 1975 4th St., San Francisco, CA 94158, USA
- Prakash Satwani
- Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
- Christa Krupski
- Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA; Cincinnati Children’s Hospital Medical Center, Cancer and Blood Disease Institute, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA
- Amy Keating
- University of Colorado, Anschutz Medical Campus, Colorado Children’s Hospital, 13123 East 16th Avenue, Aurora, CO 80045, USA
- Vanessa Fabrizio
- University of Colorado, Anschutz Medical Campus, Colorado Children’s Hospital, 13123 East 16th Avenue, Aurora, CO 80045, USA
- Vasant Chinnabhandar
- Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Ave S AO-102, Minneapolis, MN 55454, USA
- Michael Kunicki
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA
- Kevin J. Curran
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
- Crystal L. Mackall
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA; Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford Cancer Institute, 265 Campus Drive, Stanford, CA 94305, USA; Division of Blood and Bone Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Room H0101, Stanford, CA 94305-5623, USA
- Theodore W. Laetsch
- Department of Pediatrics, Children's Hospital of Philadelphia/University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
- Liora M. Schultz
- Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, 1000 Welch Road, Suite 300, Palo Alto, CA 94304, USA; Corresponding author. 1000 Welch Road, Stanford, CA 94304, USA.
- Journal volume & issue
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Vol. 65
p. 102268
Abstract
Summary: Background: Tisagenlecleucel was approved by the Food and Drug Administration (FDA) in 2017 for refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-ALL in ≥2nd relapse. Outcomes of patients receiving commercial tisagenlecleucel upon 1st relapse have yet to be established. We aimed to report real-world tisagenlecleucel utilisation patterns and outcomes across indications, specifically including patients treated in 1st relapse, an indication omitted from formal FDA approval. Methods: We conducted a retrospective analysis of real-world tisagenlecleucel utilisation patterns across 185 children and young adults treated between August 30, 2017 and March 6, 2020 from centres participating in the Pediatric Real-World CAR Consortium (PRWCC), within the United States. We described definitions of refractory B-ALL used in the real-world setting and categorised patients by reported Chimeric Antigen Receptor (CAR) T-cell indication, including refractory, 1st relapse and ≥2nd relapse B-ALL. We analysed baseline patient characteristics and post-tisagenlecleucel outcomes across defined cohorts. Findings: Thirty-six percent (n = 67) of our cohort received tisagenlecleucel following 1st relapse. Of 66 evaluable patients, 56 (85%, 95% CI 74–92%) achieved morphologic complete response. Overall-survival (OS) and event-free survival (EFS) at 1-year were 69%, (95% CI 58–82%) and 49%, (95% CI 37–64%), respectively, with survival outcomes statistically comparable to remaining patients (OS; p = 0.14, EFS; p = 0.39). Notably, toxicity was increased in this cohort, warranting further study. Interestingly, of 30 patients treated for upfront refractory disease, 23 (77%, 95% CI 58–90%) had flow cytometry and/or next-generation sequencing (NGS) minimum residual disease (MRD)-only disease at the end of induction, not meeting the historic morphologic definition of refractory. Interpretation: Our findings suggested that tisagenlecleucel response and survival rates overlap across patients treated with upfront refractory B-ALL, B-ALL ≥2nd relapse and B-ALL in 1st relapse. We additionally highlighted that definitions of refractory B-ALL are evolving beyond morphologic measures of residual disease. Funding: St. Baldrick's/Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Virginia and D.K. Ludwig Fund for Cancer Research.
