Immunotherapies have shaped the cancer research space over the past decade, proving effective for the treatment of some advanced cancers that previously had no therapeutic options. Chimeric antigen receptor T-cell (CAR T-cell) therapy is one immunotherapeutic approach that has recently garnered significant attention. In brief, CAR T-cell therapy involves removing a patient’s immune cells, altering them in a laboratory setting to make them better primed to detect and kill cancer cells, and delivering the modified cells back to the patient.
A recent study published in the New England Journal of Medicine shows exciting new evidence of the benefits of CAR T cell therapy. The study (NCT04404660) tested the treatment modality called obecabtagene autoleucel (obe-cel), a CAR T-cell therapy that recognizes CD19, a marker expressed on leukemia cells. Unlike other CAR T-cell modalities used to treat leukemia, obe-cel recognizes the CD19 marker with only “intermediate affinity” instead of the “high affinity” recognition of comparable therapies. Researchers suspected the lower affinity associated with obe-cel would correlate with reduced adverse effects experienced by patients receiving other CAR T-cell therapies.
The phase 1b-2 multicenter study, which included 153 adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), revealed promising results. Of the 127 patients who received at least one infusion of obe-cel, 77% experienced remission, with 55% achieving complete remission. The observed remission rates were significantly higher than expected, indicating notable efficacy of the treatment.
The average overall survival of 127 patients on the study was 15.6 months. The researchers estimated six- and twelve-month overall survival at 80.3% and 61.1%, respectively. High-grade adverse events, including cytokine release syndrome and neurotoxicity, only developed in a small proportion of patients. The authors note that most of the patients experiencing high-grade toxicities could be identified based on their bone marrow content.
The authors concluded that obe-cel promoted long-lasting responses in patients with ALL. These findings, combined with the minimal side effects, suggest that this approach could become a highly effective modality for treating patients with relapsed leukemia. The implications of these findings for future research and clinical practice are significant, as they could lead to an eventual shift in the standard of care for patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Sources: NEJM, Nature Med