Dr. Goy on Durable Responses With Brexu-cel in the ZUMA-2 Trial in MCL

Andre H. Goy, MD, physician in chief, Hackensack Meridian Health Oncology Care Transformation Service, chairman & chief physician officer, John Theurer Cancer Center, Lydia Pfund Chair for Lymphoma, Academic Chairman Oncology, Hackensack Meridian School of Medicine at Seton Hall University, professor of medicine, Georgetown University, discusses key findings from an assessment of durable responses in the phase 2 ZUMA-2 trial (NCT02601313) in relapsed/refractory mantle cell lymphoma (MCL).

The multicenter ZUMA-2 trial evaluated the anti-CD19 CAR T-cell therapy brexucabtagene autoleucel (Tercartus; brexu-cel) in patients with relapsed/refractory MCL who had received up to 5 prior lines of therapy, including a BTK inhibitor.

A subsequent assessment of response durability in ZUMA-2 was conducted to ascertain factors associated with long-term response to brexu-cel, Goy says. Patient and product characteristics were evaluated according to a patient’s response status 24 months after treatment, he states. Analysis of this cohort at approximately 3 years median follow-up showed that 49% of patients maintained deep and durable responses with brexu-cel, while 51% relapsed prior to data cut-off. Long-term and relapsed responders had similar patient characteristics and prognostic factors, Goy continues. Both subgroups received a median number of 3 prior lines of therapy, and a similar proportion of patients had previously received treatment with bendamustine, a proteasome inhibitor, or autologous stem cell transplant. Moreover, patients in both subgroups also displayed a similar incidence of high-risk features, including a Ki-67 proliferation index score above 30% and TP53 mutations.

However, ongoing responders demonstrated lower ECOG scores and tumor burden, as well as decreased utilization of bridging therapy, Goy notes. They had also undergone less intense regimens for previous relapses. Notably, long-term responders exhibited early and increased T-cell amplification compared with relapsed responders, which is a critical component of successful CAR T-cell therapy, Goy explains.

These findings not only reveal that ECOG score, tumor burden, and bridging therapy are potential predictive factors of patient response but indicate that relapsed responders may have experienced a higher degree of immunosuppression, Goy states. Accordingly, brexu-cel may be more effective if administered earlier in the disease course. Future research will aim to overcome this treatment resistance in early relapsed patients, Goy concludes.

Editor’s Note: Dr. Goy reports serving as a consultant or in an advisory role for Genomic Testing Cooperative, Kite, MJH Associates, Inc., Cancer Outcome Tracking Analysis, Novartis, Xcenda, Bristol Myers Squibb, OncLive Peer Exchange, Medscape, AbbVie, Celgene, Elsevier, Janssen, Rosewell Park, lloplex, Vincerx, Pharmacyclics; he is currently employed by Regional Cancer Care Associates, OMI, Genomic Testing Cooperative; he received honoraria from AstraZeneca, Kite, MJH Associates, Inc, Novartis, MorphoSys, Xcenda, Bristol Myers Squibb, OncLive Peer Exchange, Medscape, Celgene, Elsevier, Janssen, Rosewell Park, lloplex, Vincerx, Pharmacyclics; he received research funding from AstraZeneca, MorphoSys, Acerta, Hoffmann-La Roche, Genentech, Celgene, Janssen, Seattle Genetics, Verastem, Karyopharm, Infinity Pharmaceuticals, Pharmacyclics.