Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL Journal Article
| Authors: | Curran, K. J.; Margossian, S. P.; Kernan, N. A.; Silverman, L. B.; Williams, D. A.; Shukla, N.; Kobos, R.; Forlenza, C. J.; Steinherz, P.; Prockop, S.; Boulad, F.; Spitzer, B.; Cancio, M. I.; Boelens, J. J.; Kung, A. L.; Khakoo, Y.; Szenes, V.; Park, J. H.; Sauter, C. S.; Heller, G.; Wang, X.; Senechal, B.; O'Reilly, R. J.; Riviere, I.; Sadelain, M.; Brentjens, R. J. |
| Article Title: | Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL |
| Abstract: | Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multicenter clinical trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult patients (age, 1-22.5 years) with R/R B-ALL were treated with 19-28z CAR T cells. Conditioning chemotherapy included high-dose (3 g/m2) cyclophosphamide (HD-Cy) for 17 patients and low-dose (£1.5 g/m2) cyclophosphamide (LD-Cy) for 8 patients. Fifteen patients had pretreatment minimal residual disease (MRD; <5% blasts in bone marrow), and 10 patients had pretreatment morphologic evidence of disease (‡5% blasts in bone marrow). All toxicities were reversible, including severe cytokine release syndrome in 16% (4 of 25) and severe neurotoxicity in 28% (7 of 25) of patients. Treated patients were assessed for response, and, among the evaluable patients (n 5 24), response and peak CAR T-cell expansion were superior in the HD-Cy/MRD cohorts, as compared with the LD-Cy/morphologic cohorts without an increase in toxicity. Our data support the safety of CD19-specific CAR T-cell therapy for R/R B-ALL. Our data also suggest that dose intensity of conditioning chemotherapy and minimal pretreatment disease burden have a positive impact on response without a negative effect on toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01860937. © 2019 by The American Society of Hematology. |
| Keywords: | adolescent; adult; cancer chemotherapy; cancer survival; child; clinical article; treatment response; overall survival; fludarabine; prednisone; hypertension; cytarabine; drug megadose; neurotoxicity; biological marker; low drug dose; infection; bone marrow; etoposide; thrombocytopenia; cyclophosphamide; vincristine; acute lymphoblastic leukemia; disease severity; feasibility study; minimal residual disease; heart failure; multicenter study; patient safety; mental disease; seizure; headache; heart arrhythmia; childhood leukemia; leukemia relapse; tremor; ataxia; hyperreflexia; cell expansion; cd19 antigen; clofarabine; cancer morphology; cytokine release syndrome; asparaginase macrogol; disease burden; human; priority journal; article; clonus; chimeric antigen receptor t-cell immunotherapy; involuntary movement |
| Journal Title: | Blood |
| Volume: | 134 |
| Issue: | 26 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2019-12-26 |
| Start Page: | 2361 |
| End Page: | 2368 |
| Language: | English |
| DOI: | 10.1182/blood.2019001641 |
| PUBMED: | 31650176 |
| PROVIDER: | scopus |
| PMCID: | PMC6933289 |
| DOI/URL: | |
| Notes: | Erratum issued, see DOI: 10.1182/blood.2020008394 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work