CD19/CD22 CAR-T Cell Cocktail Therapy Following Autologous Transplantation in Patients with Relapsed/Refractory B-Cell Lymphomas

High-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or refractory(R/R) B-cell lymphoma. Eligibility for HDT-ASCT is based upon the presence of chemo-sensitive disease to salvage therapy. Patients with a positive PET scan prior to ASCT have a substantially inferior suvival. Furthermore, the outcomes of patients who have progressive disease after salvage treatment is extremely dismal. We hypothesized that, following HSCT, the immunosuppressive microenvironment would be diminished as a result of myeloablative conditioning and that administering CAR-T cell therapy during the hematopoietic reconstitution could eradicate posttransplant residual disease, leading to lower relapse rates after HSCT. Based on our previous work that a dual-targeting CAR T cell cocktail of sequential cell infusions targeting CD19 and CD22 may help overcome antigen escape relapse in B-cell malignancies, we therefore conducted an open-label, single-center, and single-arm pilot study of a treatment comprising the sequential infusion of CD22 and CD19 CAR-T cells following autologous hematopoietic stem cell transplantation (HSCT). We aimed to evaluate the safety and efficacy of the treatment in R/R B cell lymphoma patients with residual or progression disease after salvage treatment. Between November 14, 2016 and August 15, 2019, 42 patients underwent BEAM conditioned HDT-ASCT and followed by CAR 19 /22 T cells infusion. The overall response rate was 90.5% (95% CI, 77.4-97.3). At a median follow-up of 13.8 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 12-month PFS rate was 85.7 % (95% CI, 70.9 to 93.3). Grade 3 cytokine release syndrome (CRS) occurred in only 2 (5%) patients. 21% patients experienced any grade of neurotoxicity, 5% was severe Grade 3. All CRS and neurotoxicity were reversible. Beyond its extremely high complete response rates, the durability of remission and low toxicity of the autologous HSCT plus CD19/CD22 CAR-T cell cocktail therapy examined in this study emphasize strong potential of such myeloablative conditioning and dual-targeting approaches for R/R B-cell lymphomas.