FDA Issues Safety Alert on Tazemetostat Following Secondary Malignancy Risk

Clinical Summary:

• The FDA has issued a safety alert following updated interim data from the SYMPHONY-1 trial evaluating tazemetostat plus lenalidomide and rituximab in patients with relapsed or refractory follicular lymphoma.
• Results demonstrated that the incidence of secondary hematologic malignancies exceeded 5% with tazemetostat and included serious and life-threatening cases of myelodysplastic syndrome and acute leukemias, with associated mortality and limited resolution.
• In March 2026, Ipsen voluntarily withdrew tazemetostat from all indications and markets. This safety alert highlights the importance of ongoing safety evaluation for therapies granted accelerated approval.

The US Food and Drug Administration (FDA) issued a safety alert regarding tazemetostat (Tazverik®), citing an increased risk of hematologic second primary malignancies observed in the ongoing SYMPHONY-1 trial. 

Tazemetostat received accelerated approval in 2020 for adult patients with EZH2-mutated relapsed/refractory (R/R) follicular lymphoma (FL) who received at least 2 lines of prior therapy, as well as for patients with R/R FL who have no satisfactory treatment options. It also received accelerated approval for adult and pediatric patients 16 years of age and older with locally advanced or metastatic epithelioid sarcoma not eligible for complete resection. 

These approvals were granted under the accelerated approval pathway based on response data. At the time of approval, second primary malignancies were a recognized risk, with an incidence rate of 1.7%, and continued approval was contingent upon confirmation of clinical benefit in postmarketing studies.

This safety signal prompting this alert emerged from the ongoing phase 1b/3 SYMPHONY-1 trial, a double-blind, active-controlled study that randomized patients with R/R FL to receive either tazemetostat plus lenalidomide and rituximab or lenalidomide and rituximab alone. 

At an interim analysis, hematologic second primary malignancies were reported in 5.7% of patients treated with tazemetostat, compared with no reported cases in the control arm. The majority of events included myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), with additional cases of B-cell acute lymphoblastic leukemia (B-ALL) and clonal cytopenia of undetermined significance. 

These events were serious and life-threatening, with 3 deaths reported and most cases were unresolved at the time of analysis. Events occurred after a median treatment duration of 15.8 months, with onset as early as 7.5 months after treatment initiation and, in some cases, after treatment discontinuation. The observed incidence exceeded the rate reported at the time of initial approval.

Based on these findings, the Independent Data Monitoring Committee recommended halting enrollment in SYMPHONY-1 and discontinuation of tazemetostat in all treated patients. Ipsen subsequently initiated discontinuation of the drug in the trial and across clinical programs, with patients transitioning to standard-of-care therapy with lenalidomide plus rituximab. 

Source:

US Food and Drug Administration. FDA alerts health care providers and patients about increased risk of new blood cancers with Tazverik (tazemetostat) use; Sponsor to voluntarily withdraw product from market. Accessed on May 13, 2026. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-alerts-health-care-providers-and-patients-about-increased-risk-new-blood-cancers-tazverik