Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia
Cancer Immunology, Immunotherapy, ISSN: 1432-0851, Vol: 71, Issue: 3, Page: 689-703
2022
- 35Citations
- 46Captures
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Metrics Details
- Citations35
- Citation Indexes35
- 35
- CrossRef1
- Captures46
- Readers46
- 46
Article Description
CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, at www.clinicaltrials.gov; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, at www.chictr.org.cn). Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients’ CR rate. Risk factors related to leukemia-free survival (LFS) and overall survival (OS) were history of prior transplant, complex cytogenetics, TP53 mutation, severe CRS, neurotoxicity, and CAR-T therapy without consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Age and CAR-T cell dose did not influence LFS and OS. Patients with consolidative allo-HSCT after CAR-T therapy had a superior OS and LFS compared to those who did not. This benefit was also observed in both pediatric and adult patients as well as in patients either in high- or low-risk groups. This large study to identify risk factors of CR, LFS, and OS may help to maximize clinical outcomes of CAR-T therapy. PrécisTP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts < 5% can benefit from consolidative allo-HSCT post-CAR-T therapy.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85112110846&origin=inward; http://dx.doi.org/10.1007/s00262-021-03009-z; http://www.ncbi.nlm.nih.gov/pubmed/34365516; https://link.springer.com/10.1007/s00262-021-03009-z; https://dx.doi.org/10.1007/s00262-021-03009-z; https://link.springer.com/article/10.1007/s00262-021-03009-z
Springer Science and Business Media LLC
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