At a median follow-up of 27.1 months, the 24-month progression-free survival (PFS) rate was 39% with the CD19-targeted CAR T-cell therapy. The median PFS was 5.9 months. Moreover, 39% of patients continued to have an ongoing response, with a median duration of response that was not yet reached for those who achieved a complete remission (CR). Additionally, the median OS was not yet reached.
"This 2-year assessment demonstrates that axi-cel can induce durable remissions in a substantial proportion of patients with an acceptable long-term safety profile," lead investigator Sattva Neelapu, MD, professor of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center, said in a statement. "There also is evidence of gradual B-cell recovery in most patients with refractory large B-cell lymphoma who otherwise have limited treatment options."
In October 2017, the FDA approved axi-cel as a treatment for adults with relapsed or refractory NHL, based on findings from the ZUMA-1 trial. The study evaluated 108 patients, consisting of 101 from the phase II portion of the trial and 7 from the phase I group. In phase II, patients were enrolled into 2 cohorts consisting of those with diffuse large B-cell lymphoma (DLBCL; n = 77) and those with primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma (TFL; n = 24).
Prior to infusion of axi-cel, a conditioning regimen of fludarabine (30 mg/m2) and cyclophosphamide (500 mg/m2) was administered for 3 days. Axi-cel was administered as a single infusion of modified autologous T cells at a target dose of 2 x 106 CAR-positive T cells/kg. The treatment was manufactured successfully for 99% of patients, and 91% of patients received treatment with the CAR T-cell therapy.
The best achieved objective response rate (ORR) with axi-cel was 83% by investigator assessment and 74% by central review, with CR rates of 58% and 54%, respectively. At this analysis, 39% of patients continued to respond to therapy by investigator assessment and 36% were still responding by central review. Overall, 93% of those in response at month 12 continued to respond at 24 months.
In those with double expresser or high-grade B cell lymphoma (n = 37), the ORR was 91% and the CR rate was 70%. Overall, 48% of these patients continued to respond to therapy at the analysis.
CAR-positive T cells persisted over time in patients with ongoing responses. At the 24-month assessment, 66% of patients in response continued to have detectable CAR gene-marked T cells. B cell aplasia resolved by month 9 for most patients, with 61% having detectable B cells in the blood. By month 24, 75% of patients had detectable B cells. Overall, 31% of patients required intravenous immunoglobulins.
The investigators noted that there were no new cases of cytokine release syndrome or neurotoxicity reported following the 1-year follow-up analysis. Other grade 3/4 events did manifest, however, including grade 3 mental status change, grade 4 myelodysplastic syndrome, grade 3 lung infection, and 2 grade 3 bacteremia events. None of these events were determined to be related to axi-cel.
Grade ≥3 treatment-emergent cytopenia occurred in 86% of patients, including neutropenia (80%), thrombocytopenia (40%), and anemia (45%). There were significantly fewer cytopenias present on or after 3 months (grade ≥3 events occurred in 17% of patients).
- Neelapu SS, Ghobadi A, Jacobson CA, et al. 2-Year Follow-up and High-Risk Subset Analysis of Zuma-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Refractory Large B Cell Lymphoma. Proceedings from the 2018 ASH Annual Meeting and Exposition; December 1 to 4, 2018; San Diego, California. Abstract 2967.
- Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial [published online ahead of print, December 2, 2018]. Lancet Oncol. doi:10.1016/S1470-2045(18)30864-7