In what is believed to be the first prospective phase 2 trial to evaluate CAR T-cell therapy in first-line treatment of patients with high-risk large B-cell lymphoma, the anti-CD19 CAR T-cell product axicabtagene ciloleucel (axi-cel) was “highly effective” with a “manageable” safety profile in the single-arm ZUMA-12 trial, the investigators – led by Sattva A. Neelapu, MD, of the University of Texas M.D. Anderson Cancer Center – report in the April issue of Nature Medicine.
Forty patients were treated. Their median age was 61 years; 15 (38%) were aged 65 or older. Patients were selected based on high-risk disease features (International Prognostic Index [IPI] score of 3 to 5 and double- or triple-hit status) and dynamic risk assessment using interim positron emission tomography (PET) after two cycles of standard first-line chemoimmunotherapy; 45% of patients had stable or progressive disease at study entry, suggesting the presence of primary chemorefractory disease.
Among 37 efficacy-evaluable patients, the complete response rate (the primary outcome) was 78%; the objective response rate (a secondary endpoint) was 89%. At a median follow-up of 15.9 months, 73% of patients remained in objective response; median duration of response, event-free survival, and progression-free survival were not reached. Three patients (8%) experienced grade 3 or higher cytokine release syndrome and 9 (23%) reported neurologic events. The median time to peak CAR T-cell expansion was 8 days.
The findings “provide evidence that axi-cel is safe and highly effective as part of first-line treatment for adult patients with high-risk LBCL, including those with positive interim PET2, together with either double- or triple-hit lymphomas or with IPI score ≥3,” Neepalu and his colleagues write. “Further investigation is warranted in these patient populations to determine the benefit of axi-cel as first-line therapy compared with standard chemoimmunotherapy.”
- Neelapu SS, Dickinson M, Munoz J, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022;28(4):735-742. doi:10.1038/s41591-022-01731-4