CD19/CD22 CAR T cell Cocktail Therapy Following Autologous Transplantation in Patients with Relapsed/Refractory Aggressive B Cell Lymphomas: Combined CAR T Cell Therapy and Transplantation

ABSTRACT High-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) is the standard of care for chemo-sensitive relapsed or refractory (R/R) aggressive B-cell lymphoma. Patients with a positive PET scan prior to ASCT had poor prognosis, and those failed to achieve therapeutic response better than PR after salvage treatment are ineligible candidates for ASCT. We conducted an open label single-arm prospective clinical study to evaluate the safety and efficacy of sequential infusion of CD19/22 CAR T cells following HDT-ASCT. Eligibility for this study includes R/R aggressive B-NHL patients with FDG-PET (+) or patients with stable or progression disease after salvage treatment. Between November 14, 2016 and August 15, 2019, 42 patients underwent HDT-ASCT and followed by CD19/22 CAR-T cells infusion. Grade 3 cytokine release syndrome (CRS) occurred in only 2 patients. 21% patients experienced any grade of neurotoxicity, 5% was severe Grade 3. All CRS and neurotoxicity were reversible. The overall response rate was 90.5% (95% CI, 77.4-97.3). At a median follow-up of 24.3 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 2-year PFS rate was 83.3 % (95% CI, 68.2 to 91.7). No patients were found to be CD19 and CD22 negative at the time of progression. 97.1% and 68.6% patients with ongoing CR had consistently detectable levels of CD19 and CD22 CAR transgene at least 3 months, respectively. The median time to onset of sustained B-cell recovery was 8.2 months. The high durable CR rates and favorable safety profiles supported the strong potential of the HDT-ASCT plus CD19/CD22 CAR-T cell cocktail therapy for the suboptimal group of R/R aggressive B-NHL who are less sensitive or failed to salvage chemotherapy. These early data were encouraging and informative to future trials to further test the efficacy and safety of the ASCT plus CAR-T therapy in a larger population.