Axi-cel proves effective as first-line treatment for high-risk lymphoma
MD Anderson-led trial is the first to evaluate front-line CAR T cell therapy for high-risk LBCL
MD Anderson News Release March 21, 2022
Results from the ZUMA-12 trial led by researchers at showed that first-line treatment with axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor (CAR) T cell therapy, achieved a high rate of complete response in patients with high-risk large B-cell lymphoma (LBCL). The study was published today in , and results recently were presented at the 2021 American Society of Hematology (ASH) meeting.
Of the 40 patients treated with axi-cel, 89% had an objective response and 78% experienced complete response. The estimated overall survival rate at 12 months was 91%. At data cutoff, after median follow up of 15.9 months, 73% of patients had an ongoing response. While the median for duration of response, event-free survival and progression-free survival were not reached, 12-month estimates were 81%, 73% and 75%, respectively.
¡°Existing treatments for LBCL consist of six months of chemotherapy,¡± said , professor of Lymphoma and Myeloma. ¡°These results provide evidence that axi-cel may offer effective responses in one treatment and eliminate the need for patients to be exposed to other therapies.¡±
Axi-cel is an autologous anti-CD19 CAR T cell therapy manufactured from the patient¡¯s own T cells, which have been extracted and then reprogrammed with CAR molecules to help the T cells recognize cancer cells. The reengineered T cells are infused back into the patient to attack the cancer.
Based on the pivotal study, axi-cel was approved by the FDA in 2017 for the treatment of adults with relapsed or refractory (R/R) LBCL who already have received two or more lines of systemic therapies. The Phase II ZUMA-12 trial expands on the ZUMA-1 findings by evaluating the use of axi-cel as first-line therapy for patients with high-risk LBCL.
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, less than half of these patients 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 ¡Ý3. The treatment was well tolerated with no new safety signals.
¡°A randomized trial is necessary to confirm these results,¡± Neelapu said. ¡°I am highly encouraged that with additional studies we can move CAR T cell therapy to be the first treatment for high-risk lymphoma patients.¡±
Neelapu and his team plan to continue follow-up analyses to confirm the durability of the patients¡¯ responses to axi-cel. Additionally, more clinical trials will be necessary to definitively demonstrate whether CAR T cell therapy is more effective for high-risk LBCL patients than chemoimmunotherapy, the existing standard of care.
The study was funded by Kite Pharma, a Gilead Company. Neelapu serves as a scientific advisory board member. A complete listing of collaborating authors can be found within the paper .