Michael Bishop, MD, University of Chicago, Chicago, IL, discusses results from the Phase III BELINDA trial (NCT03570892), which assessed tisagenlecleucel (tisa-cel), a chimeric antigen receptor (CAR) T-cell therapy, in patients with aggressive B-cell non-Hodgkin lymphoma. The primary endpoint, which was event-free survival, was not met, and tisa-cel was not superior to the current standard of care. Dr Bishop highlights the time taken for the therapy to be administered, bridging therapy, and the dosage of lymphodepleting chemotherapy to be factors affecting the trial results. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Frederick Locke, MD, Moffitt Cancer Center, Tampa, FL, presents results from the Phase III ZUMA-7 trial (NCT03391466) which assessed axicabtagene ciloleucel (axi-cel), an autologous anti‑CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). 359 patients either received axi-cel or the standard of care, with the primary endpoint being event-free survival (EFS). After a 24 month follow-up, patients in the axi-cel arm demonstrated a superior EFS and overall response rate (ORR). Overall survival (OS) was additionally superior in the axi-cel arm, but was not statistically significant. The results suggest axi-cel can be a second-line treatment for r/r LBCL. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Crystal Mackall, MD, Stanford University, Stanford, CA, explains the rationale and the results from a Phase I trial investigating the safety and efficacy of a bispecific chimeric antigen receptor (CAR) T-cell targeting CD19 and CD22 in combination with chemotherapy in adult patients with recurrent or refractory B-cell malignancies (NCT03233854). Previous studies have revealed that up to two thirds of patients treated with CAR T-cell therapy relapse because of antigen modulation, either by complete loss or by downregulation of the CD19 target antigen. Monospecific CD22-directed CAR T-cells developed to overcome that challenge have shown remarkable activity in antigen loss variants of leukemia and in patients with lymphoma who have progressed after CD19-targeting CAR T-cell therapy. However, the bispecific CAR T-cells targeting both CD19 and CD22 tested in the Phase I trial were not more effective than monospecific CAR T-cells and showed good potency on CD19 but not on CD22. It is thus important to design novel strategies to deliver bispecific CAR T-cells. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.