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Effect of transplant status in CD19-targeted CAR T-cell therapy: a systematic review and meta-analysis

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Abstract

Chimeric antigen receptor (CAR) T-cell therapy has shown promise for relapsed/refractory malignancies. Many patients have undergone prior hematopoietic stem cell transplant (HSCT), yet effects of transplant status on CAR T-cell therapy efficacy and safety have not been reported. The purpose of the study is to systematically evaluate the likelihood of achieving optimum response, severe cytokine release syndrome (sCRS), and neurotoxicity in the context of CAR T-cell therapy for HSCT-naïve patients versus those with prior HSCT. Trials were identified in ClinicalTrials.gov, Cochrane Library, and PubMed, and through reference pearl growing. Included studies used CD19-directed CAR T-cells for relapsed/refractory B-lineage Acute Lymphoblastic Leukemia and B cell Chronic Lymphocytic Leukemia, enrolled both HSCT-naïve and prior-HSCT patients, and denoted transplant status with outcomes. Six studies were included for optimum response, five for sCRS incidence, and four for neurotoxicity incidence. The pooled odds ratio for optimum response was 1.57 favoring HSCT-naïve patients (95% CI 0.54–4.61), whereas the pooled odds ratios for sCRS and neurotoxicity were 1.41 (95% CI 0.51–3.94) and 1.37 (95% CI 0.28–6.77), respectively, toward HSCT-naïve patients. Odds ratios were non-statistically significant. Overall risk of bias was moderate. While pooled estimates showed an advantage among HSCT-naïve patients for achieving optimum response and increased likelihood for sCRS and neurotoxicity, findings were not statistically significant. Any differences in efficacy and safety of CAR T-cell therapy cannot be verifiably attributed to transplant status, and additional controlled trials with increased sample sizes are needed to determine whether suggestive patterns favoring HSCT-naïve patients are validated.

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Acknowledgements

The authors would like to thank Dr. Roger Strair, MD, PhD and Dr. Pranela Rameshwar, PhD, for contributing insightful comments and suggestions during the preparation of this manuscript.

Funding

This review was completed without any funding from public, commercial, or not-for-profit sources.

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Authors and Affiliations

  1. Department of Health Informatics, School of Health Professions, Rutgers, The State University of New Jersey, 65 Bergen Street, Newark, NJ, 07107, USA

    Kathleen Nagle, Barbara Tafuto & Lisa Palladino Kim

  2. Department of Interdisciplinary Studies, School of Health Professions, Rutgers, The State University of New Jersey, 65 Bergen Street, Room 353A, Newark, NJ, 07107, USA

    J. Scott Parrott

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  1. Kathleen Nagle
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  2. Barbara Tafuto
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Correspondence to Kathleen Nagle.

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Nagle, K., Tafuto, B., Palladino Kim, L. et al. Effect of transplant status in CD19-targeted CAR T-cell therapy: a systematic review and meta-analysis. Med Oncol 35, 144 (2018). https://doi.org/10.1007/s12032-018-1204-6

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