Investigating the Potency of CAR T-Cell Therapy in Relapsed/Refractory MCL

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.

RATIONALE

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).

TRIAL DESIGN

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.

REFERENCES

• 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.