Polatuzumab Vedotin-Based Regimens As Bridging Therapy before Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Diffuse Large B Cell Lymphoma

Background:

Chimeric antigen receptor T-cell therapy (CAR-T) has achieved great success in treating relapsed/refractory diffuse large B cell lymphoma (R/R-DLBCL). It was reported that 7% of patients did not survive while awaiting the completion of CAR T cell manufacturing, which underlines the need for shortening CAR-T cell production times and the potential importance of bridging therapy. The goal of bridging therapy is to prevent rapid disease progression prior to CAR-T cell infusion. Commonly used bridging therapy includes immunotherapy, chemotherapy and/or targeted therapy, and radiotherapy. However, no standard-of-care bridging therapy has been defined yet for R/R-DLBCL. Polatuzumab vedotin (POLA) has been shown effective both in the first-line setting and as salvage therapy for DLBCL. In this retrospective study, we reported the efficacy and safety profiles of POLA -based regimens as bridging therapy before CD19/ CD22 Bispecific CAR-T cell therapy for R/R-DLBCL.

Methods:

21 patients with R/R-DLBCL enrolled in a prospective clinical trial of CD19/ CD22 Bispecific CAR-T cell therapy (NCT06081478) received POLA -based regimens as bridging therapy, and herein we only reported the efficacy and safety profiles of the bridging therapy retrospectively.

Results:

21 patients with R/R-DLBCL were included in this analysis. The median age was 57 (22-77) years old, and female to male ratio was 11:10. The median prior lines of therapy was three (2-6), and 11 patients were primary refractory to all lines of therapy, and 15 patients were refractory to the last line therapy before CAR-T cell therapy. 19 patients had advanced disease and IPI score >2. Commonly used regimens include: POLA+ Mitoxantrone Hydrochloride Liposome+dexamethasone (N=10), POLA+Obinutuzumab+BTK inhibitors (N=7), and POLA+other agents (N=4). All patients received one cycle bridging therapy, and 20 patients received subsequent CAR-T cell infusion. All patients were evaluated for efficacy of the bridging therapy before lymphodepleting conditioning therapy using PET-CT or CT scan. 15 patients (71.4%) responded to this POLA-based bridging therapy, among whom three patients (14.3%) got complete remission. Five patients got stable disease, but symptoms related to DLBCL got a little relieved. Concerning the safety profiles, five patients developed grade 3-4 bone marrow suppression (neutropenia or thrombocytopenia), and one patient infected with COVID-19 and got fever. All patients recovered to less than grade 2 adverse effects before lymphodepleting conditioning therapy.

Conclusions:

POLA-based regimens seemed to be effective and tolerable as bridging therapy before CAR-T cell therapy for R/R-DLBCL patients, and our findings need verification in large cohort studies.

No relevant conflicts of interest to declare.