Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Abstract

Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. Case presentation We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. Conclusion This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.

The characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies: A systematic review

“…Here we collected 6 studies published in English that included 7 patients, 3 were diagnosed with AML, 2 with AUL (2/7), 1 with MS (1/7), and 1 presented with mixed phenotype acute leukemia (MPAL, 1/7). [ 3 , 6 , 9 , 10 , 22 , 23 ] Two other cases diagnosed with AML were excluded because of a lack detailed information. [ 24 ] The MS patient was female, and the 6 leukemia patients were male, which was similar to the female:male ratio observed for T-ALLs with the SET-CAN/NUP214 fusion gene.…”

“…New therapies, such as chimeric antigen receptor T (CAR-T) cell therapy, require further research. [ 10 ] In this systematic review, we summarized the characteristics and prognostic significance of the SET-CAN fusion gene in hematological malignancies.…”

Immunogenicity of CAR T cells in cancer therapy

“…However, in the same trial, 22/22 patients with CAR T cell-naive disease were in complete remission at this time point after receiving the CTL119 CAR T cell product 64 . Whether the relatively low rate of complete remissions in patients who received reinfusions reflects an immune response to epitopes shared between mouse and humanized CAR transgenes or is due to other mechanisms of resistance remains unknown 29,[64][65][66]149 .…”

Mixed Phenotype/Lineage Leukemia: Has Anything Changed for 2021 on Diagnosis, Classification, and Treatment?

“…A relapse was treated with chemotherapy and midostaurin followed by CAR T-cells therapy, leading to a continuing CR of 12 months post CAR-T at the time of publication. Another case of CAR T-cell therapy was reported by Li et al [ 30 ]. These authors used CAR T-cells prepared from lymphocytes of the donor who provided cells for Allo-HSCT when the patient relapsed after transplantation.…”