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Low toxicity and favorable overall survival in relapsed/refractory B-ALL following CAR T cells and CD34-selected T-cell depleted allogeneic hematopoietic cell transplant

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Abstract

To define the tolerability and outcome of allogeneic hematopoietic stem cell transplant (allo-HSCT) following CAR T-cell therapy, we retrospectively reviewed pediatric/young adult patients with relapsed/refractory B-ALL who underwent this treatment. Fifteen patients (median age 13 years; range 1–20 years) with a median potential follow-up of 39 months demonstrated 24-month cumulative incidence of relapse, cumulative incidence of TRM, and OS of 16% (95% CI: 0–37%), 20% (95% CI: 0–40%), and 80% (95% CI: 60–100%), respectively. Severe toxicity following CAR T cells did not impact OS (p = 0.27), while greater time from CAR T cells to allo-HSCT (>80 days) was associated with a decrease in OS. In comparing CD34-selected T-cell depleted (TCD; n = 9) vs unmodified (n = 6) allo-HSCT, the cumulative incidence of relapse, TRM, and OS at 24 months was 22% (95% CI: 0–49%) vs 0% (p = 0.14), 0% vs 50% [95% CI: 10–90%] (p = 0.02) and 100% vs 50% [95% CI: 10–90%] (p = 0.02). In this small cohort of patients, CAR T cells followed by a CD34-selected TCD allo-HSCT appears to result in less TRM and favorable OS when compared with unmodified allo-HSCT. There was no evidence that disease control was impacted by the type of consolidative allo-HSCT, which demonstrates the feasibility of this approach.

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Fig. 1: Cumulative incidence of treatment related mortality is lower in CD34 selected TCD cohort.
Fig. 2: Overall survival is higher in CD34 selected TCD cohort.
Fig. 3: Overall survival by time to allo-HSCT.
Fig. 4

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Acknowledgements

The authors thank the patients and families who participated in this trial; Georgia Flynn, and the Cellular Therapeutic Center at MSKCC for help with this study; Joseph Olechnowicz (Editor, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center) for editorial assistance; and Audrey Mauguen (PhD) for biostatistical support.

Funding

This work was supported by the William Lawrence and Blanche Hughes Foundation (KJC), St. Baldrick’s Foundation provided an A.V.M. Traders Scholar Award (KJC), and National Institutes of Health (NIH), National Cancer Institute (NCI) Cancer Center Support Grant (P30CA008748).

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Authors and Affiliations

  1. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Vanessa A. Fabrizio, Nancy A. Kernan, Farid Boulad, Maria Cancio, Jennifer Allen, Susan Prockop, Andromachi Scaradavou, Barbara Spitzer, Richard J. O’Reilly, Jaap Jan Boelens & Kevin J. Curran

  2. Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA

    Vanessa A. Fabrizio, Nancy A. Kernan, Farid Boulad, Maria Cancio, Susan Prockop, Andromachi Scaradavou, Barbara Spitzer, Richard J. O’Reilly & Kevin J. Curran

  3. Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Nancy A. Kernan, Farid Boulad, Richard J. O’Reilly, Renier J. Brentjens & Kevin J. Curran

  4. Department of Pediatrics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Meghan Higman

  5. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Steven P. Margossian

  6. Division of Hematology/Oncology, Boston Children’s Hospital, Boston, MA, USA

    Steven P. Margossian

  7. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Audrey Mauguen

  8. Department of Pediatric Hematology/Oncology, Yale Cancer Center, New Haven, CT, USA

    Niketa Shah

  9. Department of Pediatric Hematology/Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

    Elliot Stieglitz

  10. Department of Pediatric Hematology/Oncology, Nationwide Children’s Hospital, Columbus, OH, USA

    Nicholas Yeager

  11. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Renier J. Brentjens

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  1. Vanessa A. Fabrizio
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Contributions

VAF, FB, MC, JA, MH, SPM, AM, SP, AS, NS, BS, ES, NY, NAK, RJO'R, RJB, JJB, and KJC designed the research and performed research (treated patients/collected data); VAF, AM, and KJC analyzed the data and made the figures; VAF and KJC wrote the manuscript; and all authors critically reviewed the manuscript and approved the content.

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Correspondence to Kevin J. Curran.

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Conflict of interest

KJC has received research support from Juno Therapeutics and Novartis and has consulted, participated in advisory boards, or participated in educational seminars for Juno Therapeutics, Novartis, and Mesoblast; SPM has participated in advisory boards for Novartis; RJB is a co-founder and received royalties for Juno Therapeutics. The remaining authors declare no competing financial interests.

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Fabrizio, V.A., Kernan, N.A., Boulad, F. et al. Low toxicity and favorable overall survival in relapsed/refractory B-ALL following CAR T cells and CD34-selected T-cell depleted allogeneic hematopoietic cell transplant. Bone Marrow Transplant 55, 2160–2169 (2020). https://doi.org/10.1038/s41409-020-0926-1

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