MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation

Xin-Yue Zhang; Hai-Ping Dai; Ling Zhang; Si-Ning Liu; Yin Dai; De-Pei Wu; Xiao-Wen Tang

doi:10.2147/OTT.S324765

MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation

Onco Targets Ther. 2021 Oct 29:14:5197-5204. doi: 10.2147/OTT.S324765. eCollection 2021.

Authors

Xin-Yue Zhang^#^{1

2}, Hai-Ping Dai^#^{1

2}, Ling Zhang^{1

2}, Si-Ning Liu^{1

2}, Yin Dai^{1

2}, De-Pei Wu^{1

2}, Xiao-Wen Tang^{1

2}

Affiliations

¹ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.
² Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, People's Republic of China.

^# Contributed equally.

Abstract

EP300-ZNF384-positive B cell acute lymphoblastic leukemia (B-ALL) patients are reported to have a unique immunophenotype with high expression of CD19 and CD22, weak expression of CD20 and aberrant expression of CD13 and/or CD33, sensitivity to chemotherapy and a favorable outcome. To date, the cases of only 53 patients have been reported, albeit few reports on salvage therapy when conventional chemotherapies failed. Here, we describe two relapsed and refractory adult B-ALL patients with EP300-ZNF384 who achieved second remission through tandem CD19/CD22 CAR T-cell therapy. Grade 3 and 2 cytokine release syndrome were observed in cases 1 and 2, respectively. No immune effector cell-associated neurotoxicity syndrome was detected. Both patients underwent consolidate haploidentical hematopoietic stem cell transplantation (HSCT), and each maintained measurable residual disease-negative remission for 14 and 13 months, respectively. Our study suggests that CD19/CD22 CAR T-cell therapy bridging to allogeneic HSCT may be a viable option for EP300-ZNF384-positive B-ALL.

Keywords: CD19/CD22; EP300-ZNF384; acute lymphoblastic leukemia; chimeric antigen receptor T-cells; relapsed/refractory.

Publication types

Case Reports