Investigational Therapy in Mantle Cell Lymphoma: KTE-X19 CAR T-Cell Therapy - Episode 5
Michael Wang, MD: We did publish data about the pharmacokinetics and pharmacodynamics so far because of 2 factors: the nature of the therapy and, potentially, sample size. So far, the CAR [chimeric antigen receptor] T-cell therapy Tecartus [brexucabtagene autoleucel] has ignored all the worst prognostic factors. That means it demonstrated the same amount of response rate and duration response in low-risk and high-risk patients.
The skew toward CD8 could be a factor with prior ibrutinib. It’s a very small sample observation, and we need more time and more samples to validify this potential scientific finding.
This trial is designed to enroll only patients pretreated with a BTK [Bruton tyrosine kinase] inhibitor. Eighty percent of the patients are refractory to prior BTK therapy. About 10% of people are intolerant to BTK therapy. So the majority of the patients relapse after BTK therapy. They are refractory to BTK therapy. Based on data, we see an 87% overall response rate. The CR [complete response] rate applies to those people treated with a prior BTK therapy because that’s the nature of the study.
The most frequent toxicities include cytopenias. All the adverse events reported in the clinical trial are regardless of their relationships to starting therapy because, as I explained before, this population in this clinical trial, ZUMA-2, is a population being treated with later-line CAR T therapy. The median of patients were treated with prior, other therapies, including chemotherapies, and could induce cytopenias. Cytopenia, neutropenia, anemia, thrombocytopenia are most common.
The most common adverse events related to CAR T-cell therapy are hypotension, hypoxemia, fever, and infections. These are adequately addressed in the clinical trial, except for in the few patients who actually had a severe adverse effect. However, the majority of patients did very well. Their median time to CRS [cytokine release syndrome] and peak median time is very quick, about 1 to 2 days. Neurotoxicity usually started at day 5 to day 7, with a peak at about day 10 or day 14. This is totally consistent with other CAR T-cell products. So the benefit and the risk ratio are very favorable.
The other ongoing clinical trial is the Juno Therapeutics CAR T-cell clinical trial with a CD19. The difference between the 2 products is that the Kite Pharma product used the costimulatory molecule CD28, versus 4-1BB utilized by the Juno product. There are some comments floating around about 4-1BB being less toxic than CD28, but we cannot definitively answer that question unless there is a head-to-head comparison. Because of the population difference, and because many factors are not identical, we could not compare, directly, the toxicities between the 2 different trials. I’m not able to definitively answer that question because of the lack of the data. However, people have generally felt that they are very good trials in mantle cell lymphoma.
Transcript edited for clarity.