Investigational Therapy in Mantle Cell Lymphoma: KTE-X19 CAR T-Cell Therapy - Episode 3
Michael Wang, MD: The natural history of mantle cell lymphoma is the same as the natural history of lymphoma and myeloma overall and the same as other hematologic malignancies. What is the natural history of mantle cell lymphoma? It is a repeated cycle of remission-relapse, remission-relapse, and this can keep repeating for 5, 10, 20 cycles. Unfortunately, with each repeated cycle of relapse, the efficacy drops further. The more you treat them, the more resistant they become. At the end, efficacy drops to 0 because the resistance is almost 100%. Then we lose the patient to mantle cell lymphoma.
Neither chemotherapy or chemotherapy-free therapy can cure high-risk patients. You can put them into a remission for a period of time, but inevitably they will relapse. Every time they relapse you put them into another remission using chemotherapy, or a chemotherapy-free therapy, or targeted therapies, or a combination, or new trials, but they will relapse again.
What is our approach? Before CAR [chimeric antigen receptor] T-cell therapy, we did not really have any effective means. We used allogeneic transplantation. We were able to put some of the patients into a long-term remission but at a heavy price of mortality. The patient may not even survive the allogeneic transplant. Also, the allogeneic transplantation was not readily available to the majority of patients. Then we actually started treating the patients with CAR T-cell therapies. I’m very excited for Tecartus [brexucabtagene autoleucel] and that the CD19 Kite Pharma ZUMA-2 protocol data were used for FDA approval for relapsed mantle cell lymphoma.
This clinical trial particularly includes all-risk patients. Many patients have TP53 mutations, blastoid and pleomorphic variants, complex karyotype, and all that. The overall response is 87%, and the CR [complete response] rate is 62%. This is the basis of the FDA approval. Regarding adverse effects, we only saw CRS [cytokine release syndrome] toxicity. The neurotoxicity profile is very favorable. Overall, this brings hope to the high-risk patient population. Why? According to my ASH [American Society of Hematology Annual Meeting] presentation in December 2019, a big fraction of patients—approximately 50%—had 2-year follow-up data at that time. For about 40% of patients, the curves were flat. It looks as though fewer patients are relapsing. This is very encouraging. So far, the curve appears to be flat. Of course, at that time we had only 12 months of a median follow-up, with a fraction of people exceeding 24 months.
During this coming ASH in December, we’re going to present more follow-up data—more than 1-year. So please come to see our data at that conference, either in person or virtually.
Transcript edited for clarity.