Novel EZH1/2 dual inhibitor shows activity against relapsed/refractory T-cell lymphoma

Dual inhibition of EZH1/2 with valemetostat appears to induce responses in patients with relapsed or refractory peripheral T-cell lymphoma while having a manageable safety profile, according to the results of a single-arm phase II trial.

For the trial, researchers enrolled adult patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. The patients were treated with oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity.

The primary endpoint was CT-based objective response rate, assessed by blinded independent central review (BICR) using 2014 Lugano response criteria, for the peripheral T-cell lymphoma group. For the T-cell leukaemia/lymphoma group, the primary endpoint was the safety and tolerability of valemetostat. Safety was evaluated in all patients who received at least one dose of valemetostat.

A total of 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69.0 years, 68 percent male) and 22 patients with T-cell leukaemia/lymphoma (median age 66.5 years, 68 percent male) were included in the trial. The median follow-up was 12.3 months.

Objective response was documented in 52 of 119 evaluable patients (44 percent) in the relapsed or refractory peripheral T-cell lymphoma group.

In terms of safety, the most frequent grade 3−4 adverse events (AEs) were thrombocytopenia (23 percent in the peripheral T-cell lymphoma group and 50 percent in the adult T-cell leukaemia/lymphoma group), anaemia (19 percent and 46 percent, respectively), and neutropenia (17 percent and 18 percent, respectively).

Serious treatment-emergent AEs (TEAEs) occurred in 40 percent of patients in the peripheral T-cell lymphoma group and in 68 percent of those in the T-cell leukaemia/lymphoma group, with the serious TEAE considered to be related to treatment in 7 percent and 5 percent, respectively. There were no treatment-related deaths reported.