Axi-cel Demonstrates Durable Responses in Indolent Non-Hodgkin Lymphoma

Axicabtagene ciloleucel (axi-cel; Yescarta) continued to elicit high response rates and durable activity in patients with relapsed/refractory follicular lymphoma (FL) and marginal zone lymphoma (MZL), according to updated findings from the phase 2 ZUMA-5 trial (NCT03105336) that were presented during the 2022 Transplantation & Cellular Therapy Meetings.

In patients with FL, investigators reported a median duration of response (DOR) of 38.6 months and that 57% of efficacy-eligible patients had an ongoing response at the data cutoff of March 31, 2021. In this population, median progression-free survival (PFS) was nearly 40 months, and median overall survival (OS) was not reached (NR). The overall response rate (ORR) was 94% (79% complete response [CR] rate).

In patients with MZL, after a median of 24 months, efficacy outcomes appeared to improve with longer follow-up, with median DOR and OS not yet reached. Median PFS was 17.3 months. Investigators reported that half of the patients with MZL had an ongoing response at data cutoff. The ORR was 83% in patients with MZL (63% CR rate).

According to the ZUMA-5 trial protocol, an updated efficacy analysis was conducted when 80 or more treated patients with FL had more than 24 months of follow-up. A total of 110 efficacy-eligible patients were analyzed: 86 patients with FL and 24 patients with MZL. Safety data were reported for all 149 patients treated with axi-cel (124 patients with FL and 24 patients with MZL).

“In the primary analysis of [ZUMA-5; n = 104], the ORR was 92% and investigators reported a 74% CR rate after a 17.5-month median follow-up,” study author Julio C. Chavez, MD, an associate member in the Lymphoma Section of the Department of Malignant Hematology at Moffitt Cancer Center, in Tampa, Florida, said. “Here, we report updated clinical and pharmacologic outcomes from ZUMA-5 with 2 or more years of follow-up.” Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for the treatment of R/R large B-cell lymphoma and follicular lymphoma, both after more than 2 lines of systemic therapy.

Among patients with FL who progressed after less than 2 years after initial chemoimmunotherapy (POD24; n = 49), median DOR was 38.6 months. Median DOR was not reached in those without POD24 (n = 29). Median PFS was 39.6 months and NR in patients with and without POD24, respectively. Median time to next treatment (TTNT) was 39.6 months in all eligible patients with FL. Investigators reported that median OS was NR.

“Across key subgroups, long-term PFS rates in patients with FL were generally consistent,” Chavez said. Similarly, despite the limited sample size of the MZL population, the PFS rate at 12 months appeared to be consistent among key subgroups, including those patients treated with a prior Bruton tyrosine inhibitor.

Turning to safety, Chavez said the most common grade 3 or higher adverse events (AEs) were neutropenia (33%), decreased neutrophil count (28%), and anemia (25%). Seven percent of patients (6% in FL and 8% in MZL) experienced grade 3 or worse cytokine release syndrome (CRS) and 19% of patients (15% in FL and 36% in MZL) reported neurologic events. Chavez noted that most CRS cases (120 of 121) and neurologic events (82 of 87) of any grade resolved by data cutoff. Thirty-four percent of patients reported grade 3 or higher cytopenias 30 days or more post infusion (33% in FL and 36% in MZL), and the most common cytopenia reported was neutropenia in 29% of patients (27% in FL and 36% in MZL).

After data cutoff, grade 5 AEs occurred in 6 patients: 1 due to COVID-19 (unrelated), 1 COVID-19 pneumonia (related to axi-cel), 1 progressive multifocal leukoencephalopathy (related to axi-cel) and 2 cases of sepsis (both unrelated).

Chavez noted robust chimeric antigen receptor T-cell expansion in patients with FL and ongoing responses at 24 months than in patients who had relapsed. Pharmacokinetic findings were similar in patients with MZL.

Chavez said the long-term follow up in ZUMA-5 showed substantial and continued benefit of the CAR T-cell therapy. “Axi-cel maintained a manageable safety profile with no new safety signals,” he concluded.

Reference

Neelapu SS, Chavez JC, Sehgal AR, et al. Long-Term Follow-up Analysis of Zuma-5: a phase 2 study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (R/R) indolent non-hodgkin lymphoma (iNHL). Presented at: the 2022 Transplantation & Cellular Therapy Meetings; Salt Lake City, UT; April 23-26, 2022. Abstract 75.