|The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Treatment of relapsed/refractory indolent non-Hodgkin lymphoma (NHL) with axicabtagene ciloleucel (axi-cel) resulted in high response rates, according to results of the phase 2 ZUMA-5 study presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“Axi-cel demonstrated high rates of durable responses,” Caron Jacobson, MD, MMSc, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and presenter of the study, said. “The safety profile was manageable and appeared favorable in patients with follicular lymphoma compared with that previously reported for large B-cell lymphomas.”
There is an unmet need for novel therapies for patients with relapsed/refractory indolent NHL. Axi-cel is approved for the treatment of relapsed/refractory large B-cell lymphoma. The purpose of this study was to evaluate the efficacy and safety of axi-cel in the indolent NHL population.
The multicenter, phase 2 ZUMA-5 trial treated 146 patients with indolent NHL, including 124 with follicular lymphoma (FL) and 22 with marginal zone lymphoma (MZL), with axi-cel. All patients received cyclophosphamide and fludarabine conditioning prior to leukapheresis, and received a single infusion of the chimeric antigen receptor (CAR) T cells (CAR-T). The primary endpoint was objective response rate (ORR) among patients with FL, and secondary endpoints included complete response (CR) rates, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
At baseline, the median age of patients in the cohort was 61 years, and 57% of patients were male. The median number of prior lines of therapy was 3 (range, 1-10), with 64% of patients having received at least 3 prior treatments. The majority of patients (86%) had stage III to IV disease, 47% had a FLIPI score of at least 3, and 49% had high tumor bulk.
The MZL cohort was considered exploratory and was still accruing at the time of data analysis.
Axi-cel resulted in high response rates, with an ORR of 92% among evaluable patients after a median follow-up of 17.5 months. The CR rate was 76%. The ORR was higher in the FL cohort at 94%; the ORR among patients with MZL was 85%, though the sample size was smaller.
The median DOR was not yet reached, and 62% of patients had ongoing responses at data cutoff.
PFS and OS were also not yet reached. The 1-year PFS and OS rates were 73.7% and 92.9%, respectively, among all patients. The 1-year PFS rate among patients with FL was 77.5% and 45.1% in the MZL cohort. The 1-year OS was similar between the cohorts (92.8% and 92.9% for FL and MZL, respectively).
Overall, 86% of patients experienced a grade 3 or higher adverse event (AE), with the most common including cytopenias and infections. Grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity occurred among 7% and 19% of patients, respectively, most of which resolved by data cutoff. One patient died of multisystem organ failure attributable to CRS.
Cell expansion after axi-cel infusion was a median of 9 days (range, 8-371 days), and 78% of evaluable patients had low detectable levels at 12 months. A higher peak level of CAR T-cell expansion was associated with better response at 12 months. Peak CAR T-cell levels were also associated with the development of grade 3 or higher CRS and neurotoxicity.
Dr Jacobson concluded that “axi-cel may be a highly promising therapeutic approach for patients with relapsed/refractory indolent NHL.”
Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.
Jacobson C, Chavez JC, Sehgal AR, et al. Primary analysis of Zuma-5: a phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (r/r) indolent non-Hodgkin lymphoma (iNHL). Presented at: 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-9, 2020. Abstract 700.