As reported in the journal Blood by Sattva S. Neelapu, MD, and colleagues, 5-year outcomes from the the phase II ZUMA-1 trial showed that axicabtagene ciloleucel was associated with maintained response in one-third of patients with refractory large B-cell lymphoma. The estimated 5-year overall survival rate with axicabtagene ciloleucel was 42.6%.
The trial supported the October 2017 accelerated approval of axicabtagene ciloleucel for patients with relapsed or refractory large B-cell lymphoma who had received two or more lines of systemic therapy.
Sattva S. Neelapu, MD
Study Details and Key Findings
In the trial, 101 patients received lymphodepleting chemotherapy followed by an axicabtagene ciloleucel infusion at a target dose of 2 × 106 cells/kg. Median follow-up for the current analysis was 63.1 months.
In the initial analysis of the trial, the objective response rate was 83%, with complete response in 58% of patients. At data cutoff for the current analysis, responses were ongoing in 31% of patients, including ongoing complete response in 30%.
Median event-free survival was 5.7 months (95% confidence interval [CI] = 3.1–13.9 months), with a 5-year rate of 30.3% (95% CI = 21.5%–39.6%). Median progression-free survival was 5.9 months (95% CI = 3.3–15.0 months), with a 5-year rate of 31.8% (95% CI = 22.9%–41.1%).
Median overall survival was 25.8 months (95% CI = 12.8 months to not estimable), with a 5-year rate of 42.6% (95% CI = 32.8%–51.9%). Among patients with complete response, median overall survival was not reached (95% CI = 63.4 months to not estimable), with a 5-year rate of 64.4% (95% CI = 50.8%–75.1%). Median disease-specific survival was not reached (95% CI = 15.4 months to not estimable), with a 5-year rate of 51.0% (95% CI = 40.4%–60.6%).
In an analysis of 23 patients with an ongoing response at 3 years with available data, peripheral blood B cells were detectable in all, with polyclonal B-cell recovery in 91%. Among 97 patients with available data, median peak chimeric antigen receptor T-cell levels were higher in those with an ongoing response at 5 years (65.76 cells/μL) compared with those who relapsed (35.27 cells/μL) or did not achieve response (12.08 cells/μL).
No new treatment-related serious adverse events or deaths were observed during follow-up.
The investigators concluded: “[T]his 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory large B-cell lymphoma. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axicabtagene ciloleucel in a subset of patients with aggressive B-cell lymphomas.”
Dr. Neelapu, of the Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Blood article.
Disclosure: The study was funded by Kite, a Gilead Company. For full disclosures of the study authors, visit ashpublications.org/blood.
