The Phase II ZUMA-12 trial expands on the ZUMA-1 findings by evaluating the use of axicabtagene ciloleucel (axi-cel) as first-line therapy for patients with high-risk large B-cell lymphoma (LBCL).
In this study, axi-cel demonstrated a high rate of rapid and complete responses in a population with high, unmet need.
Neelapu presented the results from this study at ASH 2021.
“ZUMA-12 is the first study of front-line CAR T cell therapy for high-risk LBCL, and we look forward to confirming the results in a randomized trial,” Neelapu said. “Although additional studies are needed, this study shows axi-cel to be effective and suggests patients may receive durable benefit from receiving the treatment before being exposed to other therapies.”
High-risk LBCL is a subgroup of the disease in which patients have double- or triple-hit lymphoma or additional clinical risk factors identified by the International Prognostic Index (IPI) or interim positron emission tomography (PET) scan.
Historically, around half of these patients do not achieve long-term disease remission with typical treatment approaches like chemoimmunotherapy.
Forty patients with high-risk LBCL were enrolled and treated with axi-cel.
Ninety-five percent had stage III/IV disease, 25% had double or triple-hit status per central assessment, and 78% had an IPI score ≥3.
The treatment was well tolerated with no new safety signals.
The analysis showed that 89% of patients treated with axi-cel experienced an objective response, and 78% had complete response.
At data cutoff, 73% of patients had an ongoing response after median follow-up of 15.9 months.
Medians for DOR, event-free survival (EFS), and PFS were not reached; 12-month estimates were 81%, 73% and 75%, respectively.
The estimated OS at 12 months was 91%.
The investigators plan to conduct continued follow-up to confirm durability of the patients’ responses to the treatment.
Additional clinical trials are needed to definitively demonstrate that CAR T cell therapy is superior to existing standard of care with chemoimmunotherapy in these high-risk patients.