FDA Warns of New Blood Cancers With Sarcoma, Lymphoma Drug

The FDA on Monday alerted clinicians about the risk of new primary hematologic malignancies in patients treated with tazemetostat (Tazverik), a sarcoma and lymphoma drug now being pulled from global markets.

The risk was known when the EZH2 inhibitor was granted accelerated approvals in 2020, with an incidence of 1.7%. But new data from the SYMPHONY-1 trial found a rate approaching 6% over a median treatment duration of 15.8 months.

“It was determined that the risks of treatment with Tazverik outweigh its benefits,” the FDA said.

Of the 318 follicular lymphoma patients in the randomized study — evaluating lenalidomide (Revlimid) and rituximab with or without tazemetostat — 18 patients (5.7%) developed a second hematologic malignancy in the tazemetostat arm versus none in the control arm. Three died and the new malignancies remain unresolved for 14 patients.

Most of the cases were myelodysplastic syndromes (MDS) or acute myeloid leukemia, while others included B-cell acute lymphoblastic leukemia and clonal cytopenia of undetermined significance.

“Treatment-emergent acute leukemias and MDS are serious and life-threatening disorders that are not expected to be reversible,” the FDA stated.

Trial participants had been taking the drug for 1 to 3 years, and the new malignancies started as early as 7.5 months after beginning tazemetostat, while some occurred after treatment cessation.

Drugmaker Ipsen announced the U.S. and global withdrawal of tazemetostat in March based on the emerging safety concern. An independent data monitoring committee recommended that all trial participants discontinue tazemetostat immediately, but SYMPHONY-1 will remain open for long-term safety follow-up. Ipsen has discontinued all other active trials of the EZH2 inhibitor and any expanded access programs.

Tazemetostat originally received accelerated approvals from the FDA for metastatic or locally advanced epithelioid sarcoma and for previously treated follicular lymphoma in patients with an EZH2 mutation. As always, drugs approved under the pathway are subject to confirmation of clinical benefit.