Long-term remission in patients with Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL) has been achieved through a novel treatment approach combining CAR T-cell therapy and autologous stem cell transplant (ASCT). This study, published in Cancer, presents a promising strategy for patients who cannot undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) or decline it. The research, conducted at a single center, focused on a sequential 'sandwich' approach using CD22/CD19 chimeric antigen receptor (CAR) T-cell therapy followed by ASCT.
The study's primary objective was to evaluate the overall survival of patients with Ph-negative B-ALL who received this innovative treatment. The results were impressive, with a median overall survival (OS) and leukemia-free survival (LFS) that had not yet been reached at the time of the study's median follow-up of 28 months. The 2-year OS rate was an astonishing 97%, and the 2-year LFS rate was 72%. These findings indicate a high degree of success in achieving deep and durable remissions.
The study's methodology involved a phase 2, single-arm, open-label design, approved by the institutional review board of the First Affiliated Hospital of Soochow University. It enrolled newly diagnosed adolescent/young adult (AYA) and adult patients with Ph-negative B-ALL who had CD19 and CD22 expression by multiparameter flow cytometry (MFC). The patients were either unable to undergo allo-HSCT or declined it.
The treatment protocol included induction and consolidation chemotherapy before CAR T-cell therapy. After induction and lymphocyte recovery, peripheral blood lymphocytes were collected and used to manufacture CAR T cells. The CD22- and CD19-directed CAR T cells were infused sequentially at a specific dose. Autologous stem cell mobilization and collection followed, followed by conditioning and ASCT. A second course of CD22/CD19 CAR T cells was administered after ASCT.
The safety profile of this treatment was generally consistent with the expected toxicities of CAR T-cell therapy and high-intensity chemotherapy. All patients experienced grade 3/4 hematologic toxicities, but no severe organ toxicity or unexpected signals were reported. Cytokine release syndrome (CRS) was generally mild, and no cases of grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome were observed. B-cell aplasia, a marker of CAR T-cell activity, was noted in all patients.
This study highlights a potential breakthrough in treating Ph-negative B-ALL, offering a promising approach for patients who cannot undergo allo-HSCT. However, the authors emphasize the need for further validation and exploration of allo-HSCT-free strategies through larger studies with longer follow-up periods.
