According to results from the ZUMA-2 trial presented at the 2019 ASH Annual Meeting, 93% of patients with relapsed/refractory mantle cell lymphoma (MCL) responded to treatment with KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. The investigational agent's safety profile also was consistent with that reported with prior studies of anti-CD19 CAR T-cell therapies, noted lead investigator Michael L. Wang, MD, from the University of Texas MD Anderson Cancer Center.
The response rate seen in this trial "is the highest reported rate of disease response in patients with prior Bruton tyrosine kinase (BTK) inhibitor failure," with a 67% complete remission (CR) rate, Dr. Wang said.
The ZUMA-2 trial enrolled adults with relapsed/refractory MCL who had received up to 5 prior lines of therapy, which had to have included an anti-CD20 antibody, chemotherapy, and a BTK inhibitor. All participants also had an Eastern Cooperative Oncology Group performance status of 0 to 1.
A total of 74 patients were enrolled. Participants underwent conditioning with a chemotherapy regimen of cyclophosphamide 300 mg/m2 per day and fludarabine 30 mg/m2 for 3 days prior to KTE-X19 therapy. The study protocol also allowed patients to receive bridging therapy during the CAR T-cell manufacturing process, according to investigator's discretion, which could include ibrutinib, acalabrutinib, or dexamethasone. Patients then received a single infusion of KTE-X19 at a target dose of 2Ã—106 CAR T cells/kg, and tumor response was first assessed 28 days after treatment.
At the time of data cutoff (July 24, 2019), 68 patients had received KTE-X19, representing a 92% manufacturing success rate. Dr. Wang reported safety results for all treated patients and efficacy findings for the first 60 treated patients.
Participants' median age was 65 years (range = 38-79), and more than half of patients had intermediate or high-risk disease (n=38; 56%), per the Mantle Cell Lymphoma International Prognostic Index.
After a median follow-up of 12.3 months (range = 7.0-32.3), the objective response rate (defined as CR or partial response [PR]) was 93%, including:
- 40 CRs (67%)
- 16 PRs (27%)
In addition, several participants who initially experienced a PR or stable disease eventually converted to CR (n=24; 40%).
Dr. Wang reported that responses occurred rapidly after KTE-X19 infusion, with a median time to response of 1 month (range = 0.8-3.1 months). Responses also were durable: The median duration of response had not been reached at the end of follow-up (range = 8.6 months to not estimable). Among evaluable patients, 57% remained in remission at data cutoff. Both median progression-free survival (PFS) and overall survival (OS) were not reached during the study follow-up period; 12-month PFS and OS rates were 61% and 83%, respectively.
The most frequently reported treatment-related adverse events (AEs) included pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypertension (51%). Two grade 5 AEs were seen: 1 case of pneumonia related to conditioning chemotherapy and 1 case of staphylococcal bacteremia related to the CAR T-cell infusion.
The AEs observed with KTE-X19 in ZUMA-2 were similar to those seen with trials of FDA-approved CAR T-cell therapies in patients with aggressive non-Hodgkin lymphoma, the study authors noted. This included cytokine release syndrome (CRS) in 62 participants (91%), which occurred at a median of 2 days after KTE-X19 administration (range = 1-13 days). However, Dr. Wang added, all cases of CRS resolved and there were no grade 5 events observed. There also were no grade 5 neurologic toxicities observed.
The high response rates suggest a role for KTE-X19 in relapsed/refractory MCL, and Dr. Wang said that he is "cautiously optimistic" about these results. Longer-term follow-up is needed to confirm the study findings, which also are limited by the trial's single-arm design.
The authors report relationships with Gilead Sciences, which sponsored the trial.
Wang ML, Munoz J, Goy A, et al. KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients (Pts) With Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Results of the Phase 2 ZUMA-2 Study. Abstract #754. Presented at the 2019 ASH Annual Meeting, December 9, 2019; Orlando, FL.