At that time, study coauthor Brian Hill, MD, a lymphoma specialist at the Cleveland Clinic, said: “I believe that the high overall response rate will translate into prolonged overall survival.” Dr Chavez, who was not involved in the study, called the high response rates seen and the durability of those responses “compelling.”
But in the most recent update of ZUMA-2, presented in NEJM in the intention-to-treat population of 74 patients who were enrolled in the trial, the objective response rate was slightly lower — 85% of the patients had an objective response. “This percentage of patients with a response, which includes 59% of those with a complete response, after a single infusion is promising in this population of patients,” the authors of the NEJM update added.
Although a total of 74 patients were enrolled in the trial and underwent leukapheresis, KTE-X19 was successfully manufactured for 71 patients (96%) and was only administered to 68 individuals (92%).
A total of 3 patients for whom the manufacturing of KTE-X19 failed did not proceed to an additional apheresis as a result of deep-vein thrombosis, death from progressive disease, or withdrawal of consent. “Two patients who had successful manufacture of KTE-X19 died from progressive disease before the receipt of conditioning chemotherapy. After the receipt of conditioning chemotherapy, 1 patient with ongoing atrial fibrillation, an exclusion criterion, was deemed to be ineligible for KTE-X19 infusion,” wrote the study authors in NEJM.
Secondary endpoints included the duration of response, progression-free survival (PFS), overall survival (OS), the percentage of patients with an investigator-assessed objective response, the incidence of adverse events, the levels of CAR-T cells in blood and cytokines in serum, and changes in scores from baseline to month 6 in the 5-level version of the European Quality of Life–5 Dimensions (EQ-5D) questionnaire.
As of May 30, 2018, the 12-month rates of PFS and OS were 71% (95% CI, 50-84) and 86% (95% CI, 66-94), respectively, according to the abstract reported at the February 2020 meeting. But according to the March 2020 NEJM report, at 12 months, the estimated PFS and OS were 61% and 83%, respectively — lower survival rates than were previously reported. In all, at a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission.
But, among the 56 patients who had a response to CAR-T therapy (out of the 60 total patients included in the primary efficacy analysis), progressive disease developed in 14 individuals. Two patients who had disease progression after having an objective response to KTE-X19 received a second infusion approximately 1 year and 1.3 years after the initial infusion. A total of 16 patients (24%) of the 68 patients who received KTE-X19 died, primarily from progressive disease (14 patients). Two patients (3%) had grade 5 adverse events; 1 of these reactions was deemed to be related to conditioning chemotherapy, while the other was deemed to be related to the combination of the conditioning chemotherapy and KTE-X19 therapy.
In addition, side effects were common, and were serious in 68% of those who were treated. Adverse events of grade 3 or higher occurred in 99% of the 68 treated patients; 91% of patients experienced cytokine release syndrome, but none of these cases were fatal and were managed with medications.
Although the rates of grade 3 or higher neutropenia and/or thrombocytopenia were also high (85% and 51%, respectively), they were “not unexpected,” said Dr Chavez. “It just underscores the fact that CAR-T therapy is effective in MCL but requires expertise and a team approach.”
Nonetheless, despite the fact that some seemingly durable remissions were seen in this difficult-to-treat population with MCL, the trial therapy led to “serious and life-threatening toxic events,” wrote the authors. They added, however, that these events are generally consistent with what has been seen in previous studies of anti-CD19 CAR-T in aggressive B-cell lymphomas.
Additional reporting by Randi Hernandez.
Disclosure: The original study was supported by Kite, a Gilead company. For a full list of disclosures, please refer to the original study.
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