Q: Can you briefly describe the mechanism of action of tazemetostat?
Tazemetostat is a novel, first-in-class EZH2 inhibitor that is approved for follicular lymphoma. EZH2 is a histone methyltransferase that is abundant in the germinal center where follicular lymphoma originates. In about 20% of follicular lymphoma cases, EZH2 is mutated. Tazemetostat is known to inhibit this mutated form of EZH2. What's unique is that tazemetostat can also inhibit the wild-type form, which is abundantly prevalent in the germinal center, as well, so we found that there is activity in both mutated EZH2 as well as wild-type [disease]. It's worthwhile to note that response rates are higher in those with mutated EZH2.
Q: What are some of the biggest concerns with the drug's toxicity profile? Have any new safety concerns become more apparent with its use in the real-world treatment setting as opposed to what was seen in clinical trials?
In the clinical trial that garnered its approval by the FDA, tazemetostat was really well tolerated. Most toxicities were low-grade to grade 1/2--things like nausea and abdominal pain, [along with] some upper respiratory tract infections and other gastrointestinal disturbances. Overall, there were low rates of grade 3/4 toxicities, so this is a well-tolerated agent. [However, because] this agent was [just] approved [about] a year ago, we still have a lot of information to gather about what some of its long-term toxicities may be in the real-world setting.
Q: How does tazemetostat's toxicity profile compare with those of other available agents?
In comparison with other treatment options--primarily other oral treatment options, such as the PI3K inhibitors, including idelalisib [Zydelig], duvelisib [Copiktra], copanlisib [Aliqopa], and even umbralisib [Ukoniq]--tazemeto-stat has a pretty favorable safety profile. We don't have to...