Axicabtagene ciloleucel (axi-cel; Yescarta), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was previously approved for the treatment of patients with certain types of large B-cell lymphoma who had not responded to other therapies. This success led investigators to test the treatment in patients with relapsed or refractory mantle cell lymphoma (R/R MCL), a rare B-cell non-Hodgkin lymphoma that affects 4200 new patients in the United States each year.1
Patients with MCL frequently fail several therapy options and often do not live as long as a year. Their average survival is about 8 months.
Results of the ZUMA-1 phase I/ II trial (NCT02348216) presented at the 2017 AACR Annual Meeting showed an objective response rate of 82%, with a complete response (CR) rate of 54%; after 8.7 months of follow-up, 39% of patients remained in CR.2
In phase II of the ZUMA-1 clinical trial, axi-cel demonstrated promising activity in patients with large B-cell lymphomas. Updated long-term results showed that axi-cel induced an objective response rate of 82%, with a CR rate of 58%.3
The value of axi-cel in treating R/R MCL will be tested in the multicenter phase II ZUMA-2 clinical trial (NCT02601313).
Patients will receive a fixed dosage of fludarabine and cyclophosphamide– conditioning chemotherapy daily, followed by a single infusion of axi-cel administered intravenously. The primary endpoint of the trial is the overall response rate, with duration of response, best objective response, and progression-free survival as secondary endpoints.
WHO IS ELIGIBLE?
The phase II Zuma-2 trial will enroll about 130 patients with an ECOG performance score of 0 or 1 who have received no more than 5 prior therapies. Eligible participants must have received an anthracycline- or bendamustine-containing chemothe-rapy, anti-CD20 monoclonal antibody therapy, and Bruton’s tyrosine kinase inhibitor therapy with ibrutinib (Imbruvica) or acalabrutinib (Calquence).
MCL is an aggressive and often incurable disease, and much hope and expectation rests on axi-cel for success in this trial. Results from ZUMA-2 could be available in 2019.
- Mantle cell lymphoma facts. Leukemia & Lymphoma Society website. lls.org/sites/default/files/file_assets/mantlecelllymphoma.pdf. Updated November 2014. Accessed August 1, 2018.
- Locke FL, Neelapu SS, Bartlett NL, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (Axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). Presented at: 2017 AACR Annual Meeting; April 1-5, 2017; Washington, DC. Abstract CT019. cancerres.aacrjournals.org/content/77/13_Supplement/CT019.
- Neelapu SS, Locke FL, Bartlett NL, et al. Long-term follow-up ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). Presented at: ASH Annual Meeting and Exposition; December 9-12, 2017; Atlanta, GA. Abstract 578. bloodjournal.org/content/130/Suppl_1/578?sso-checked=true.