Tandem CD19/CD22 CAR-T cells conquer high-risk cytogenetics and acquire complete remission in r/r B-ALL patients

Abstract

Abstract Background CD19 chimeric antigen receptor T cells (CAR-T cells) have demonstrated impressive response rates in relapse and refractory B acute lymphoblastic leukemia (r/r B-ALL). However, a high rate of patients suffered a CD19-negative (CD19−) relapse, and confers dismal outcomes. Dual targets approaches are proved to optimize the response rate and prevent antigen negative relapse. While for r/r B-ALL patients, whether it would show better outcome than CD19 CAR-T, is still not clear. Methods We conducted an open label, single center clinical trial at the First Affiliated Hospital of Soochow University to investigate the efficacy and safety of tandem CD19/CD22 dual targets CAR-T cells for r/r B-ALL. Results A total of 47 r/r B-ALL patients with high-risk cytogenetics, such as TP53 alteration, Philadelphia Chromosome positive (Ph+) ALL with T315I mutation and Ph-like ALL, received CD19/CD22 CAR-T therapy from 2017 October to 2021 June. Severe cytokine release syndrome occurred in 8 of 47 patients (17.02%). The immune effector cell-associated neurotoxicity syndrome (ICANS) and macrophage release syndrome (MAS) were rare observed. Hematologic complete remission (CR) was observed in 47/47 (100%) and 40/47 (85.1%) patients achieved minimal residual disease negative (MRD-) CR. At a median follow up of 24.83 months (range, 2.57 to 50.67), overall survival was 93.56% (95% CI, 81.36–97.8%) at 6 months, 80.51% (95% CI, 65.88–89.35%) at 1 year. Twelve patients relapsed post CAR-T infusion and only 2 of 12 had CD19- recurrence. The leukemia free survival (LFS) rate and cumulative incidence of relapse at 1 year was 74.47% (95% CI, 59.44–84.61%) and 19.66% (95% CI, 4.36–42.68%), respectively. High-risk cytogenetics did not affect the long long-term survival. The multivariable Cox regression analyses showed that better long-term LFS was associated with MRD-CR status post CAR-T, as well as bridging hematopoietic stem cell transplantation (HSCT). Conclusions Tandem CD19/CD22 CAR-T cells are safety and effective for patients with high-risk cytogenetics. Allo-HSCT can provide long-term durable disease control in these patients. Trial Registration: ClinicalTrials.gov identifier: NCT 03614858