Novel Drugs Look Promising in the Treatment of Follicular Lymphoma

One recently approved drug and two that are being tested in clinical trials are poised to open up new treatment options to patients with follicular lymphoma through the targeting of disease-driving genetic alterations in cancer cells.

Dr. Germame Ajebo, assistant professor of medicine at Georgia Cancer Center at Augusta University, shared information on the future of treatment options during the recent virtual CURE® Educated Patient Leukemia & Lymphoma Summit.

In his talk, Ajebo focused on drugs meant for use in disease that has recurred or become resistant to previous treatments.

Follicular lymphoma is a usually slow-growing form of the blood cancer non-Hodgkin lymphoma in which tumor cells grow as groups to form nodules. Treatment can consist of a watch-and-wait strategy in asymptomatic cases, but when disease causes troublesome symptoms or shows signs of spread, therapy should consist of radiation or drugs targeting the protein CD20, sometimes with chemotherapy, Ajebo said.

But how should the disease be treated if those strategies and subsequent targeted drugs don’t work?

One new strategy, he noted, was approved by the FDA to treat the disease in June 2020: Tazverik (tazemetostat) is a targeted drug that inhibits the activity of the cancer-fueling protein EZH2, which is present in 20% of follicular lymphomas. The phase 2 trial that led to its approval included 45 patients who had the genetic mutation that generates the protein and 54 patients who did not.

In patients with the mutation, he said, researchers found an objective response rate (combining all partial and complete responses) of 78%, with 9% of patients responding completely and 22% maintaining stable disease. Among 54 patients without the mutation, researchers found an objective response rate of 33%, including a complete response rate of 6% and stable and progressive disease rates of 30% each.

Tazverik is approved for previously treated patients who have recurrent or resistant EZH2-mutation positive follicular lymphoma or have no satisfactory alternative treatment options.

An experimental option, Ajebo said, is mosunetuzumab, which works by simultaneously inhibiting the proteins CD3 and CD20, thus activating T cells that work to kill cancer cells.

In a phase 1/1b clinical trial, he said, mosunetuzumab was found to induce complete remissions in patients with non-Hodgkin lymphoma and a poor prognosis, including those who had not fared well on CAR-T cell therapies. In that trial, the objective response rate was 43.8% and the complete remission rate was 25%.

Read more: Mosunetuzumab Produces Complete Remissions in Patients with Non-Hodgkin Lymphoma.

About 29% of patients experienced cytokine release syndrome, in which the immune system attacks healthy organs, Ajebo said. Other side effects of any severity included neutropenia (a blood count problem), fatigue, hypophosphatemia (a blood electrolyte issue), diarrhea, fever, nausea and headache. Serious or severe side effects were neutropenia, hypophosphatemia and anemia.

A drug that hits the same two targets, REGN1979, also showed promising results in a phase 1 trial. Among 43 patients, Ajebo said, the objective response rate was 95% and the complete response rate was 75%.

“These are out there on the horizon, and once they have been well-studied, they can be brought into frontline treatment,” Ajebo said. “These options are hopefully things to look at and expect approvals in the near future.”

He added that “tazemetostat and other bispecific antibodies will possibly be considerations to look at in patients who progress on multiple lines of therapy for follicular lymphoma.”

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