By Cecilia Brown - Last Updated: March 8, 2024
Axicabtagene ciloleucel (axi-cel) led to “continued durable responses” in patients with relapsed or refractory indolent non-Hodgkin lymphoma, according to three-year follow-up data from the ZUMA-5 trial.
The study was led by Sattva Neelapu, MD, of the University of Texas MD Anderson Cancer Center, and published in Blood.
The multicenter, single-arm phase II trial evaluated axi-cel, an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with follicular lymphoma (FL, n=127) or marginal zone lymphoma (MZL, n=31) who received at least two prior lines of therapy.
Of those patients, 152 received axi-cel, including 124 patients with FL and 28 with MZL. Patients underwent leukapheresis followed by conditioning chemotherapy and an axi-cel infusion of 2 × 106 CAR T-cells/kg. The study’s primary endpoint was the overall response rate (ORR).
At a median follow-up of 41.7 months in FL and 31.8 months in MZL, the ORR and complete response (CR) rates were “comparable with that of the primary analysis,” Dr. Neelapu and colleagues wrote. The ORR and CR rates for FL were 94% and 79%, respectively, while the ORR and CR rates for MZL were 77% and 65%, respectively.
The overall median duration of response was 38.6 months. In patients with FL, the median duration of response was 38.6 months, while it was not reached in patients with MZL. The median duration of response was not reached in patients with a complete response but was 4.9 months in patients who had a partial response.
The overall median progression-free survival (PFS) was 40.2 months. In patients with FL, the median PFS was 40.2 months, and not reached in patients with MZL. The estimated 36-month PFS was “consistent among patients with FL, regardless of other high-risk characteristics,” according to Dr. Neelapu and colleagues. The median time to next treatment and the median overall survival (OS) was also not reached.
The peak CAR T-cell levels were higher in patients who had ongoing responses at 36 months (53.9 cells/µL) than in those who relapsed (29.6 cells/µL) or in patients who did not respond to the therapy (22.2 cells/µL).
Grade 3 or higher adverse events (AEs) of interest that occurred among treated patients since the two-year analysis were “largely in recently enrolled patients with MZL” and included one neurologic event, five cytopenias, and two infections.
Eight patients died due to an AE, and five died due to second primary malignancies unrelated to axi-cel. After the data cutoff date, deaths from AEs considered related to axi-cel included one death due to COVID-19 pneumonia and one due to progressive multifocal leukoencephalopathy, both occurring in patients with FL.
“After three years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond two years, and manageable safety in patients with [relapsed or refractory indolent non-Hodgkin lymphoma],” Dr. Neelapu and colleagues concluded. “Late progression events or deaths related to axi-cel or lymphodepleting therapy were uncommon…no new safety signals were observed among treated patients with either FL or MZL since the prior analysis.”
Reference
Neelapu SS, Chavez JC, Sehgal AR, et al. Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5). Blood. 2024. doi.org/10.1182/blood.2023021243
Original Source: Axicabtagene Ciloleucel Leads to ‘Continued Durable Responses’ in Indolent B-Cell Lymphoma in ZUMA-5 | Blood Cancers Today