Abstract
A recently reported clinical trial indicates that the EZH2 inhibitor tazemetostat is effective against relapsed or refractory follicular lymphoma. Three of 28 patients with EZH2 mutations had complete responses, and 17 had partial responses.
The investigational drug tazemetostat (Epizyme) triggers responses in 71% of patients with relapsed or refractory follicular lymphoma who carry mutations in EZH2, according to a study recently presented at the 23rd European Hematology Association (EHA) Congress in Stockholm, Sweden.
EZH2 regulates gene expression by controlling histone methylation. The gene is mutated in about 20% to 25% of patients with follicular lymphoma, and these alterations may drive the cancer by preventing B cells from completely differentiating. Clinical trials are testing tazemetostat, which blocks EZH2, against a variety of cancers, including mesothelioma and non–small cell lung cancer.
Gilles Salles, MD, PhD, of Lyon-Sud Hospital Centre in Pierre-Bénite, France, and colleagues are performing a phase II trial of the drug in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. At the EHA Congress, the researchers presented interim results for 82 patients with follicular lymphoma.
The scientists sorted the patients into two groups based on whether they carried EZH2 mutations. Of the 28 patients who had the mutations, 71% responded: Three showed a complete response and 17 showed a partial response, none of whom developed progressive disease. Eight had stable disease. Neither the median progression-free survival nor the median duration of response had been reached.
The drug was less effective in the 54 patients who lacked EZH2 mutations. The objective response rate in this group was 33%. Three patients had complete responses, and 15 showed partial responses. In contrast to the EZH2-mutant group, 31% of patients developed progressive disease, but 31% did experience stable disease.
Although current trial participants can continue to receive the drug, additional patients cannot be enrolled in the trial—at least for now. The FDA halted accrual for all tazemetostat studies after a child with chordoma in a separate trial of the drug developed T-cell lymphoma; Epizyme is trying to determine the cause. Salles notes that no patients in the current trial developed the disease. The most common adverse effect was nausea, which affected 22% of the patients. Eighteen percent of the patients reported fatigue, and 17% developed anemia.
“We are quite excited about these [efficacy] results,” says Salles. “The activity of the drug in patients with mutant EZH2 is remarkable.”
Loretta Nastoupil, MD, of The University of Texas MD Anderson Cancer Center in Houston, who wasn't connected to the research, says that “the study looks quite promising,” adding that the drug is “potentially a rational way to target the biology of the disease.” The study also supports using EZH2 status as a biomarker to identify patients who might benefit from the drug, she says. –Mitch Leslie
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