A novel chimeric antigen receptor (CAR) T-cell therapy has shown encouraging results for patients with mantle cell lymphoma with disease refractory to Bruton’s tyrosine kinase (BTK) inhibition therapy. The phase 2 findings revealed 61% progression-free survival and 83% overall survival a median of 12 months after treatment with the novel KTE-X19 CAR T-cell therapy (N Engl J Med 2020;382[14]:1331-1342. doi: 10.1056/NEJMoa1914347).
“This percentage of patients with a response … after a single infusion is promising in this population of patients,” according to the authors, led by Michael Wang, MD, a professor of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, in Houston.
In their phase 2 trial, named ZUMA-2, Dr. Wang and researchers at 20 sites across the United States and Europe enrolled 74 adults with relapsed or refractory mantle cell lymphoma to receive one infusion of KTE-X19, being developed by Kite Pharma. Most patients had been treated with at least three—and up to five—previous therapies, and all had received a prior BTK inhibitor, either ibrutinib (Imbruvica, Pharmacyclics) or acalabrutinib (Calquence, AstraZeneca). Eighty-eight percent of patients had no response or lost response to BTK inhibitor therapy, and the remainder either relapsed after discontinuing BTK treatment or experienced intolerable adverse events (AEs).
After undergoing leukapheresis, Dr. Wang’s team administered optional bridging therapy in the 37% of study participants who had a high disease burden, giving them a glucocorticoid alone or in combination with ibrutinib or acalabrutinib. Most bridging therapy recipients had an increase in disease burden despite the treatment, the authors reported. After leukapheresis and bridging therapy, patients were given conditioning chemotherapy and a single infusion of KTE-X19. The protocol determined that a primary efficacy analysis would be conducted after 60 patients were treated and followed for seven months.
KTE-X19 was manufactured for 71 patients, 68 of whom received the treatment a median of 16 days after leukapheresis. Of the six patients who did not receive the CAR T-cell therapy, three had deep vein thrombosis, one died due to progressive disease, one withdrew from the study, and one had ongoing atrial fibrillation and was deemed ineligible.
Dr. Wang’s team reported that among 60 patients in the prespecified primary efficacy analysis, 93% (95% CI, 84%-98%) and 67% (95% CI, 53%-78%) experienced objective and complete treatment responses, respectively, six months after infusion. The median time to initial response was one month, and the median time to complete response was three months.
After a median 12.3 months (range, seven to 32.3 months), 57% of those in the primary efficacy analysis were in remission, and the estimated progression-free and overall survival were 61% and 83%, respectively. By the final prepublication cutoff date, 78% of those who had an initial complete response were in remission and 76% of all the patients were alive. There were no differences in rates of response between subgroups of patients.
In an intention-to-treat analysis at six months that included all 74 enrolled patients, 85% had an objective response and 59% had a complete response.
The most common grade 3 or higher AEs were neutropenias, thrombocytopenias and anemia, which occurred in 94% of the 68 treated patients. Other common grade 3 or higher AEs included infections, which 32% experienced; cytokine release syndrome, which occurred in 15%; and neurologic events, which occurred in 31% of patients. There were no treatment-related deaths.
The authors concluded that the “trial showed that a single infusion of KTE-X19 was capable of inducing durable remissions in patients with relapsed or refractory mantle-cell lymphoma after the failure of BTK inhibitor therapy.”
In a press release from MD Anderson, Dr. Wang noted that “although this study continues, [the] results, including a manageable safety profile, point to this therapy as an effective and viable option for patients.”
—David Wild