Autologus stem cell transplantation as bridging rherapy followed by CD19 Car-T cells in relapsed refractory large B cell lymphoma

Peripheral blood autologous stem cell transplantation (PBSCT) is considered the standard consolidation treatment for refractory aggressive large B cell lymphoma (LBCL) in first complete remission (CR) [1], and it may also have a role for patients with chemosensitive LBCL without CR [2]. Additionally, PBSCT alone was retrospectively associated with better outcomes compared to chimeric antigen receptor T cell therapy (CAR-T) in patients with LBCL with partial remission (PR) after salvage therapy [3], despite ZUMA-7 trial may have recently suggested differently [4]. Nowadays, third-line standard treatment is based on CAR-T cells. The addition of a bridging therapy may be necessary to contain the disease progression. As lower disease burden assessed before CAR-T cells infusion is associated with better outcomes [5] and prior studies have established that tandem autologous–allogeneic stem cell transplantation is feasible and provides satisfactory outcomes in patients with high-risk LBCL [6, 7], we reasoned that in patients receiving CAR-T cells, PBSCT might provide better disease debulking than conventional bridging regimens and thereby lead to greater efficacy of subsequent CAR-T cell therapy. In our clinical practice, we have proposed the use of autologous PBSCT as a bridging therapy prior to infusion of CAR-T cells to six patients with very high-risk NHL and available frozen autologous stem cells. To date, there are no published data on the use of PBSCT as a bridge to CAR-T cell therapy. All patients described have provided informed consent to non-interventional anonymized use of their clinical data. At the time of relapse or refractoriness after two lines of therapy, patients were determined eligible for CAR-T, and lymphocyte apheresis was scheduled. After lymphocyte collection, patients were admitted for PBSCT. The conditioning regimen in all patients was FEAM: Fotemustine (150 mg/m2 , days −7 and −6), cytarabine (400 mg/m2 , days −5 to −2), etoposide (200 mg/m2 , days −5 to −2) and melphalan (140 mg/m2 , day −1). Shortly after discharge from PBSCT, patients were admitted for CAR-T. Patient characteristics, disease status at transplants and celltherapies oucomes are shown in Table 1 and were analyzed with descriptive statistics (Pearson test and Mann Whitney / Wilcoxon rank sum test) and Kaplan-Meier curves. We calculated survival outcomes were calculated from the day 0 of CAR-T cells therapy.