Incidence of CD19-negative relapse after CD19-targeted immunotherapy in R/R BCP acute lymphoblastic leukemia: a review

Abstract

There are inconsistencies in the reporting of CD19 antigen status following treatment with CD19-targeted therapies. A majority of evidence comes from studies reporting small sample sizes. In this review, we systematically summarize published studies that have reported rates of CD19-negative relapse after treatment with either blinatumomab or CD19-directed CAR T-cell therapy and report the rates of CD19-negative relapse when evaluated in a standardized way across trials. CD19-negative relapse appears to occur more commonly in relapses following CAR T-cell therapy compared with blinatumomab, whether proportions are calculated among all treated patients (8.7% vs 4.5%) or among patients who relapse (30% vs 22.5%). The median (range) duration of follow-up was 29.3 (17.4-50.8) and 20.4 (6.9-49.0) months for publications on blinatumomab (n = 10) and CAR T-cell therapies (n = 23), respectively. There is a need for standardized reporting of CD19 antigen status in the setting of relapse following novel immunotherapies to inform clinical practice.

Keywords:

• Acute lymphoblastic leukemia
• blinatumomab
• CAR T-cell therapy
• CD19-negative relapse

Acknowledgments

The authors thank Hemant Jethwani for assistance with the literature search and identification of eligible articles and Advait A. Joshi, Ph.D., of Cactus Life Sciences (part of Cactus Communications) for data extraction and manuscript revision. L.G. is the Ergen Family Chair in Pediatric Oncology at Children’s Hospital Colorado.

Author contributions

BA, TT and KV designed the study; BA and TT conducted the literature search, extracted, and analyzed data from published studies; BA wrote the first draft of the manuscript; FL, BS, TT, KV, BA, IA, LG, DH, RB, NB, JHP, and HK reviewed and interpreted the results, participated in the drafting of the manuscript, and read, revised, and approved the final manuscript.

Disclosure statement

L.G. is an unpaid advisor to Amgen, Janssen, Kura, Novartis, OnKure, and Syndax for development of oncology drug products and the use of such in pediatric patients. L.G. discloses family stock interests in Mirati and Sanofi Paris. I.A. serves on advisory boards for Amgen, Kite, Pfizer, Jazz, AbbVie, Agios, and Sobi; is a consultant for Pfizer and Amgen; and has received research support from MacroGenics and AbbVie. F.L. was a member of the Board of Directors or Advisory Committee for Amgen, Bellicum, and Novartis; served as a consultant for Bluebird Bio, Bellicum, and Novartis; and received honoraria from Miltenyi and Amgen. B.S. reports honoraria from Pharmacyclics, Janssen, Acrotech, Spectrum, BeiGene, and Gilead Sciences; a consultancy or advisory role for Adaptive Biotechnologies, Bristol Myers Squibb/Celgene, Novartis, Pfizer, Amgen, Precision Biosciences, and Kite, a Gilead Company; research funding from Incyte, Jazz Pharmaceuticals, Gilead Sciences, and Kite; and travel support from Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, Stemline Therapeutics, and Kite. R.B. has received honoraria and has served on advisory boards for Amgen, Pfizer, Shire, and Incyte. H.K. reports research funding from AbbVie, Agios Pharmaceuticals, Amgen, Ariad Pharmaceuticals, Astex Pharmaceuticals, Bristol-Myers Squibb, Cyclacel Pharmaceuticals, Daiichi-Sankyo, ImmunoGen, Jazz Pharmaceuticals, Novartis, and Pfizer and honoraria from AbbVie, Actinium Pharmaceuticals, Agios Pharmaceuticals, Amgen, ImmunoGen, Orsenix, Pfizer, and Takeda. J.H.P. reports a consultancy or advisory role for Kite, Novartis, Amgen, InCyte, Allogene, Autolus, Artiva, Intellia, Servier, Pfizer, Takeda, and AstraZeneca and research funding from Genentech, Amgen, and Juno Therapeutics. T.T., B.A., and K.V. are employees and stockholders of Amgen. D.H. and N.B. declare no conflict of interest.

Additional information

Funding

This study was funded by Amgen Inc.