OncoTargets and Therapy (Oct 2021)
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
Abstract
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 Tang1,2 1National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 2Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, People’s Republic of China*These authors contributed equally to this workCorrespondence: De-Pei Wu; Xiao-Wen TangDepartment of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, People’s Republic of ChinaTel +8651267781856Fax +8651265113556Email [email protected]; [email protected]: 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: chimeric antigen receptor T-cells, CD19/CD22, EP300-ZNF384, acute lymphoblastic leukemia, relapsed/refractory
