Lymphoma Subgroup Experiences Durable Responses from Kymriah Treatment

Treatment with chimeric antigen receptor (CAR)-T cell therapy showed encouraging rates of durable responses among adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated data from the pivotal JULIET trial.

Researchers saw an overall response rate (ORR) of 52 percent after a median follow-up of 14 months in patients treated with Kymriah (tisagenlecleucel), which is a type of CAR-T cell therapy that uses the patient’s own T cells to fight the cancer.

“In this patient population we have a very high unmet medical need. Overall survival is short, (with a poor prognosis) of about four months,” Peter Borchmann M.D., from the Department of Internal Medicine at the University Hospital of Cologne in Germany, said in an interview with CURE.

The current standard of care for patients with DLBCL — the most common form of non-Hodgkin lymphoma — is high-dose chemotherapy followed by autologous stem cell transplant (ASCT). However, Borchmann said this therapy has its own set of challenges.

“We aim at high-dose chemotherapy and stem cell transplantation; however, efficacy is not very good and toxicity is extremely high,” he said. “If you compare this intervention to CAR-T cell therapy, as we have seen it in the JULIET trial, the risk-to-benefit ratio seems to be clearly better for CAR-T cell therapy.”

In the multicenter, global phase 2 study — presented at the 2018 European Hematology Association (EHA) Congress in Stockholm, Sweden – 93 patients were evaluable for efficacy and 111 patients for safety.

Overall, 40 percent of patients who were followed for at least three months, or discontinued earlier, experienced a complete response. Of the patients with a complete response at month three, 83 percent stayed in complete response at the one-year mark. In addition, 12 percent of patients had a partial response, and median duration of response was not reached.

The median overall survival (OS) among all infused patients was 11.7 months, with a 12-month OS rate of 49 percent. Median OS was not reached for patients in complete response, and the 12-month OS rate was 95 percent for these patients.

“In all responding patients, we can follow the gene signature of the CAR-T cell for up to two years indicating that there’s ongoing efficacy just by this one single infusion,” Borchmann said.

Although CAR-T cell therapy shows promise in the oncology field, it comes with serious side effects. Cytokine release syndrome (CRS), sometimes called a cytokine storm, can be life-threatening. It occurs when too many cytokines are released into the blood from the immune cells affected by the therapy. Neurological events can also occur. These may include language impairment, confusion, hallucinations, unresponsiveness and seizures.

In the JULIET trial, grade 3/4 CRS and neurological toxicities occurred in 22 percent and 12 percent of patients, respectively.

Initial study findings presented in December 2017 reported three patient deaths from disease progression. Updated data showed no additional deaths.

Kymriah was the first approved CAR-T cell therapy in the United States, with the Food and Drug Administration (FDA) giving it the green light in August 2017. It was first indicated for use in patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.

In May 2018, based on earlier findings from the JULIET study, the FDA approved Kymriah for use in adult patients with relapsed/refractory large B-cell lymphoma, including DLBCL, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma, after two or more lines of systemic therapy.

Looking toward the future of treatment for patients, Borchmann would like to see Kymriah used earlier in the process.