Patients with MCL Who Exhausted Treatment Options Have a Potential New Therapy

Treatment with the chimeric antigen receptor (CAR)-T cell therapy KTE-X19 demonstrated durable responses, making it a significant improvement for patients with mantle cell lymphoma (MCL), according to Dr. Ian W. Flinn.

“MCL is a relatively uncommon lymphoma, so there are not that many patients with MCL every year who would be eligible. However, we are getting durable remissions from this therapy. It is going to have an important role in patient management,” Flinn, director of Lymphoma Research at Sarah Cannon Research Institute, said in an interview with Targeted Oncology^®, a sister publication of CURE’s.

“This is an important study because it is in a patient population that has exhausted standard therapies and in whom outcomes are generally poor,” he added. “The eligibility criteria included prior treatment with a BTK inhibitor. The expected outcome in this patient population is a response rate in the neighborhood of 25% to 40% with survival around six to nine months. It’s truly a patient population in need of new therapies.”

Therefore, in the pivotal, multicenter phase 2 ZUMA-2 trial, researchers evaluated the efficacy and safety of KTE-X19 in patients with relapsed/refractory MCL, who had one to five prior lines of therapy. In the trial, patients had to have received Imbruvica (ibrutinib) or Calquence (acalabrutinib).

“I think that this points out how difficult of a patient population this is,” Flinn explained. “Unfortunately, when patients who had a prior ibrutinib or acalabrutinib treatment progress, they tend to progress very quickly and become quite ill. It is often challenging to get these patients onto a clinical trial, which is one of the hurdles with this study.”

In total, 68 patients received KTE-X19. They were a median age of 65 years and were predominantly men and were diagnosed with stage 4 disease.

After a median follow-up of 12.3 months, 47% of patients had been followed for at least 24 months.

Patients demonstrated an objective response rate (ORR) of 93%, with 40% of patients who initially had a partial response or stable disease and transitioned to a complete response over a median three months.

At the time of analysis, the median duration of response had not yet been reached, but of those who achieved a complete response, 78% of patients remained in remission at the time of analysis. For the first 28 patients who were treated with the CAR-T cell therapy, the median follow-up was 27 months, whereas 43% of the responders remained in remission. The 12-month progression-free survival (the time from treatment to disease progression or worsening) rate was 61%, and the 12-month overall survival rate was 83%.

“This is a significant improvement for patients with MCL, and it is hard to really articulate that in words,” said Flinn. “Compared to what you would expect for this patient population, this therapy is an exciting advancement.”

Overall, 63% of patients experienced any grade neurotoxicity, including 31% who had a grade 3 or greater neurotoxicity event. Cytokine release syndrome (CRS) was also a concern for the CAR-T cell therapy and occurred in 91% of patients, of which 15% were at least grade 3 in severity. There were no grade 5 cases of neurotoxicity or CRS with the treatment of KTE-X19.

“The investigators are hopeful that this will lead to (a Food and Drug Administration) approval and ultimately commercial availability. We will have to wait to see if that comes to fruition,” Flinn said. “Ultimately, treating patients in this very refractory state is a setup for having the worst result in terms of (side effects) and response rates. Despite these challenges, these response rates and durations of response are really remarkable. However, if we are going to advance this therapy, we need to move it earlier in the natural history of this disease. Many of the investigators would like to move this earlier, perhaps as a second-line therapy rather than a third-line therapy and perhaps earlier than that.”

This article originally appeared on TargetedOnc.com, titled “Flinn Examines Improved Response Rates with KTE-X19 in Mantle Cell Lymphoma.”