In a phase II trial (VALENTINE-PTCL01) reported in The Lancet Oncology, Zinzani et al found that valemetostat—a novel dual inhibitor of EZH1 and EZH2—was active in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
Study Details
In the trial, 133 patients with relapsed or refractory PTCL and 22 patients with adult T-cell leukemia/lymphoma were enrolled between June 2021 and August 2022 from sites in 12 countries across Asia, Europe, North America, and Oceania. Patients received oral valemetostat at 200 mg daily in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary outcome measure for patients with PTCL computed tomography–based objective response on blinded independent central review. The primary outcome measure among patients with adult T-cell leukemia/lymphoma was safety/tolerability.
Key Findings
Median follow-up was 12.3 months. Among 199 evaluable patients with PTCL, 52 (44%, 95% confidence interval [CI] = 35%–53%) had an objective response, including a complete response in 17 (14%). Stable disease was achieved in an additional 21 patients (18%). The median duration of response was 11.9 months (95% CI = 7.8 months to not evaluable). Among the 119 patients, median progression-free survival was 5.5 months (95% CI = 3.5–8.3 months), and median overall survival was 17.0 months (95% CI = 13.5 months to not evaluable).
In the safety populations of patients with PTCL (n = 133) and adult T-cell leukemia group (n = 22), the most common grade 3 or 4 adverse events were thrombocytopenia (23% and 50%), anemia (19% and 46%), and neutropenia (17% and 18%). Serious adverse events occurred in 40% and 68% of patients, respectively, with serious treatment-related adverse events in 7% and 5%. No treatment-related deaths were observed.
The investigators concluded: “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.”
Pier Luigi Zinzani, MD, of the Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Institute of Hematology “L. e A. Seragnoli,” University of Bologna, Italy, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Daiichi Sankyo. For full disclosures of the study authors, visit thelancet.com.
