Valemetostat, a novel dual inhibitor of EZH1 and EZH2, has demonstrated promising activity in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), according to results from a phase II trial (VALENTINE-PTCL01). The study, led by Pier Luigi Zinzani, MD, from the University of Bologna, Italy, and published in The Lancet Oncology, highlights the potential of valemetostat as a treatment option for this challenging patient population.
The international, multicenter trial enrolled 133 patients with relapsed or refractory PTCL and 22 patients with adult T-cell leukemia/lymphoma across sites in Asia, Europe, North America, and Oceania between June 2021 and August 2022. Participants received 200 mg of oral valemetostat daily in continuous 28-day cycles until disease progression or unacceptable toxicity.
Efficacy and Outcomes
The primary outcome measure for patients with PTCL was objective response based on computed tomography assessments by blinded independent central review. With a median follow-up of 12.3 months, the study found that among 119 evaluable patients with PTCL, 52 (44%, 95% CI = 35%–53%) achieved an objective response, including 17 (14%) who experienced a complete response. An additional 21 patients (18%) achieved stable disease. The median duration of response was 11.9 months (95% CI = 7.8 months to not evaluable). The median progression-free survival was 5.5 months (95% CI = 3.5–8.3 months), and the median overall survival was 17.0 months (95% CI = 13.5 months to not evaluable).
Safety Profile
The safety analysis included 133 patients with PTCL and 22 patients with adult T-cell leukemia/lymphoma. The most common grade 3 or 4 adverse events were thrombocytopenia (23% and 50%, respectively), anemia (19% and 46%, respectively), and neutropenia (17% and 18%, respectively). Serious adverse events occurred in 40% and 68% of patients, respectively, with serious treatment-related adverse events in 7% and 5%. Notably, no treatment-related deaths were observed.
Investigator Conclusions
"These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile," the investigators concluded.
The study was funded by Daiichi Sankyo. Full disclosures of the study authors are available at the Lancet Oncology website.
