Clinical Benefit, Limited Adverse Events From CAR-T Therapy for NHL
Long-term data show that a chimeric antigen receptor T-cell (CAR-T) therapy induces significant clinical benefit without added adverse events among patients with refractory aggressive non-Hodgkin lymphoma.
Frederick Locke, MD, department of blood and marrow transplant, cellular immunotherapy program, Moffitt Cancer Center (Tampa, FL) presented the long-term follow-up results of the ZUMA-1 clinical trial at the 2018 BMT Tandem Meetings (February 21-25; Salt Lake City, UT). The primary analysis of ZUMA-1 analyzed the effects of the CAR-T therapy axicabtagene ciloleucel in patients with refractory non-Hodgkin lymphoma and showed an overall response rate (ORR) of 82% with a manageable safety profile.
Dr Locke and colleagues conducted a 1-year follow-up analysis, which combined data from seven patients from the phase 1 portion and 101 patients from the phase 2 portion. Patients presented with refractory diffuse large B-cell lymphoma, transformed follicular lymphoma, or primary mediastinal large B-cell lymphoma. All patients had previously received anti-CD20 therapy and an anthracycline-containing regimen.
After a median follow-up of 15.4 months, Dr Locke and colleagues found the ORR to be 82% in the combined analysis, with 58% of patients achieving complete response.
“Importantly, in the updated analysis, 23 out of 60 patients, or over a third of patients who had either a partial response or stable disease at the first tumor assessment 1 month after infusion, subsequently achieved a complete response up to 15 months post-infusion without additional therapy,” Dr Locke said in his presentation.
The median time to conversion from partial to complete response was 64 days (range, 49-424), which indicates that regular follow-up rather than consolidative therapy is an appropriate action for patients with stable disease or partial response to CAR-T therapy.
Dr Locke reported that 97% of patients experienced a grade 3 or higher adverse event, most of which were hematologic related and associated with chemotherapy. Twelve percent of patients had grade 3 or higher cytokine release syndrome (CRS), 31% had a grade 3 or higher neurologic event, and 8% of patients had IV immunoglobin G support at any point during the study.
However, since the primary analysis and 6 months of additional follow-up, Dr Locke and colleagues have reported no new cases of therapy-related CRS, neurologic events, or grade 5 adverse events.
In his concluding remarks, Dr Locke asserted that axicabtagene ciloleucel is “highly effective in patients with large B-cell lymphoma who otherwise have no curative options.”—Zachary Bessette