CD22-targeted chimeric antigen receptor-modified T cells for children and adults with relapse of B-cell acute lymphoblastic leukemia after CD19-directed immunotherapy.

作者信息

Myers Regina M, DiNofia Amanda M, Li Yimei, Diorio Caroline, Liu Hongyan, Wertheim Gerald, Fraietta Joseph A, Gonzalez Vanessa, Plesa Gabriela, Siegel Donald L, Iannone Emma, Shinehouse Laura, Brogdon Jennifer L, Taylor Clare, Jadlowsky Julie K, Hexner Elizabeth O, Engels Boris, Baniewicz Diane, Callahan Colleen, Ruella Marco, Aplenc Richard, Barz Leahy Allison, McClory Susan E, Rheingold Susan R, Wray Lisa, June Carl H, Maude Shannon L, Frey Noelle V, Grupp Stephan A

机构信息

Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

出版信息

J Immunother Cancer. 2025 Apr 17;13(4):e011549. doi: 10.1136/jitc-2025-011549.

DOI:10.1136/jitc-2025-011549

PMID:40246579

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12007026/

Abstract

BACKGROUND

Relapse of B-cell acute lymphoblastic leukemia (B-ALL) with CD19-antigen loss after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has a dismal prognosis. Novel immunotherapeutic strategies for this patient population are urgently needed.

METHODS

We tested a novel, fully human anti-CD22/4-1BB CAR T-cell construct, CART22-65s, in parallel phase I studies for pediatric and adult B-ALL. After lymphodepletion, CART22-65s was infused using a 3-day fractionated dosing scheme, allowing for omission of the second and third doses in cases of early cytokine release syndrome (CRS).

RESULTS

Twenty-two patients, all with relapse after prior CD19-directed immunotherapy, were enrolled. Of 19 infused patients (pediatric, n=17; adult, n=2), 14 (74%) achieved a complete remission (CR), including 4 of 6 (67%) patients refractory to prior inotuzumab. Five of 14 patients in a CR proceeded to consolidative hematopoietic cell transplantation (HCT). With a median follow-up of 38 months, the 12-month relapse-free survival rate was 38.4% (95% CI 19.3% to 76.5%) and overall survival rate was 52.6% (95% CI 34.3% to 80.6%). Two patients received additional CART22-65s treatments for subsequent CD22-positive relapses; one achieved another CR. All CRS (n=17, 89%) and neurotoxicity (n=4, 21%) events after initial infusion were grades 1-2. The only grade 3 CRS/neurotoxicity and the only high-grade immune effector cell-associated hemophagocytic lymphohistocytosis-like syndrome occurred in the retreatment setting. In vivo cellular kinetic data revealed robust CART22-65s proliferation by quantitative PCR peaking at a median of 20 days postinfusion, with the cells persisting out to month 42 in one patient who achieved a long-term remission with CART22-65s alone.

CONCLUSIONS

The favorable safety profile and high remission rates in exceedingly refractory B-ALL support the continued development of CART22-65s but also highlight the need to use the product in combination with HCT or other novel strategies.