Results from the ZUMA-II trial indicated that patients with relapsed/refractory mantle cell lymphoma (MCL) resistant to prior therapies may benefit from treatment with KTE-X19, an autologous CD19-targeting CAR T-cell therapy.1
Findings from this trial were presented on December 9, 2019 at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida.
In this multi-center phase II cohort of 74 patients, 93% of patients responded to the CAR T-cell therapy, with 67% of participants achieving a complete response (CR). Currently, this is the highest reported rate of disease response in patients with prior BTK inhibitor failure.
“Outcomes for patients whose disease progresses following initial treatment is poor. Our study demonstrated significant and durable clinical benefit for patients with relapsed or refractory mantle cell lymphoma for which there are no curative treatment options,” Michael Wang, MD, professor of lymphoma & myeloma at the University of Texas MD Anderson Cancer Center, said in a press release.2
Adults with relapsed/refractory MCL who received up to five prior lines of therapy, including an anti-CD20 antibody, chemotherapy, and a BTK inhibitor, were enrolled in the ZUMA-II trial. All participants also had an Eastern Cooperative Oncology Group performance status of 0 to 1.
Patients underwent leukapheresis, followed by conditioning with a chemotherapy regimen of cyclophosphamide 300 mg/m2 per day and fludarabine 30 mg/m2 for 3 days. Study protocol also allowed patients to receive bridging therapy during the CAR T-cell manufacturing process, which could include ibrutinib, acalabrutinib, or dexamethasone. Patients then received a single fusion of KTE-X19 at a target dose of 2x106 CAR T cells/kg, and tumor response was first assessed 28 days after treatment.
As of data cutoff (July 24, 2019), 68 patients had received KTE-X19, representing a 92% manufacturing success rate. Safety results for all treated patients and efficacy findings for the first 60 treated patients were reported.
Wang noted that responses occurred rapidly after KTE-X19 infusion, with a median time to response of 1 month (range, 0.8-3.1 months). Responses were also durable; the median duration of response had not been reached at the end of follow-up (8.6 months – not estimable). Fifty-seven percent of all evaluable patients, as well as 78% of those with a CR, remained in remission at data cutoff.
Moreover, these high response rates also appeared to translate to high survival rates. Both median progression-free survival (PFS) and overall survival (OS) were not reached, while 12-month PFS and OS rates were 61% and 83%, respectively.
The most commonly reported treatment-related adverse events (AEs) included pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypertension (51%). Two grade 5 AEs were seen – one case of pneumonia related to conditioning chemotherapy, and one case of staphylococcal bacteremia related to the CAR T-cell infusion.
The AEs observed for KTE-X19 were similar to those seen with trials of FDA-approved CAR T-cell therapies in patients with aggressive non-Hodgkin lymphoma, according to the researchers.
“ZUMA-II is the first multi-center, phase II study of CAR T-cell therapy for relapsed/refractory mantle cell lymphoma, and these interim efficacy and safety results are encouraging,” Wang said. “Although this study continues, our reported results, including a manageable safety profile, point to this therapy as an effective and viable option for patients with relapsed or refractory mantle cell lymphoma.”
Longer-term follow-up is needed to confirm the study findings, which are also limited by the trial’s single-arm design.
1. KTE-X19: A CAR T-Cell Option for Mantle Cell Lymphoma? [news release]. Orlando, Florida. Published December 10, 2019. ashclinicalnews.org/on-location/ash-annual-meeting/kte-x19-car-t-cell-option-mantle-cell-lymphoma/. Accessed December 11, 2019.
2. CAR T-cell therapy effective for relapsed mantle cell lymphoma patients [news release]. Houston, Texas. Published December 4, 2019. newswise.com/articles/car-t-cell-therapy-effective-for-relapsed-mantle-cell-lymphoma-patients?sc=sphr&xy=10021790. Accessed December 11, 2019.