Chimeric antigen receptor (CAR) T cells trigger complete remissions (CR) that can last a median of 2 years in patients with certain types of follicular lymphoma (FL), a new phase I/II trial shows. The results bolster preliminary findings that the therapy is effective for this type of cancer.
Some early CAR T-cell trials included patients with FL and found that such therapy yielded remissions. Alexandre Hirayama, MD, of the Fred Hutchinson Cancer Research Center in Seattle, WA, and colleagues performed a further test of the therapy with 21 patients: eight with relapsed or refractory FL and 13 with disease that had undergone histologic transformation to diffuse large B-cell lymphoma (DLBCL). The patients received a lymphodepleting regimen followed by CAR T-cell infusions. (Although patients with transformed disease are now eligible for tisagenlecleucel [Kymriah; Novartis] and axicabtagene ciloleucel [Yescarta; Kite Pharma], these CAR T-cell therapies hadn't been approved when the trial started.)
Like tisagenlecleucel and axicabtagene ciloleucel, the CAR T cells that the patients received in the study carry an antibody fragment that targets CD19 on B cells. The cells in the study have the same costimulatory molecule as tisagenlecleucel. However, the therapy tested by Hirayama and colleagues differed in that it included a 1:1 ratio of CD4+ to CD8+ T cells.
The researchers found that 88% of the patients with FL achieved a CR within 42 days. After a median follow-up of 24 months, all of them were still in remission. These results are similar to those from a trial of tisagenlecleucel in refractory B-cell lymphomas, which found a CR rate of 71% in 14 patients with FL.
In addition, CRs occurred in 46% of patients with histologically transformed disease. No patients had relapsed after 15.6 months, with durable remissions lasting up to 39 months. The CR rate for this group is comparable to that in other studies in which patients with DLBCL received an approved CAR T-cell product. In ZUMA-1, for instance, 58% of patients with DLBCL achieved a CR after infusions of axicabtagene ciloleucel, including patients with histologically transformed disease.
Two side effects commonly caused by CAR T-cell infusions—cytokine release syndrome (CRS) and neurotoxicity—occurred in both groups of patients. Half of the patients with FL developed CRS, compared with 39% of those with transformed disease, and 50% of the patients with FL experienced neurotoxicity, versus 23% with transformed disease. However, none developed CRS or neurotoxicity more severe than grade 2.
Patients with FL who relapse within 2 years of their first treatment with chemoimmunotherapy have a 5-year survival of 50%. The results of the new study “could change the paradigm for treatments of this population,” says Hirayama. He adds that researchers will learn more about the effectiveness of this approach from other ongoing phase II trials.
“These early data are exciting,” says Nirav Shah, MD, of the Medical College of Wisconsin in Milwaukee, who wasn't connected to the research. “But it has to be validated in a larger patient population,” he adds. “The question is whether this will translate to a cure some day.”
Most of the patients in the study would be expected to relapse within 2 years with other treatments, says Edward Copelan, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, NC, who also wasn't connected to the research. “This is a high-risk group. To have such a high remission rate and what appear to be prolonged remissions is very encouraging.” –Mitch Leslie
- ©2019 American Association for Cancer Research.
Volume 9, Issue 9
