Valemetostat Among Patients With R/R Aggressive Adult T-Cell Leukemia/Lymphoma

Results from a Phase 2 Trial

According to findings from a phase 2 trial recently published in Blood, valemetostat, a selective dual inhibitor of EZH2 and EZH1 with strong antitumor properties, demonstrated promising efficacy and tolerability among patients with relapsed/refractory (R/R) aggressive adult T-cell leukemia/lymphoma (ATL), achieving a high overall response rate and a manageable safety profile. 

Study authors explain that despite new agents being incorporated into the treatment of ATL, “response rates in patients with aggressive ATLs remain low, and patients continue to experience relapse.” In an attempt to increase response rates and tolerability, Koji Izutsu, MD, National Cancer Center Hospital, Tokyo, Japan, and coauthors aimed to assess the efficacy and safety profile of valemetostat among patients with R/R ATL. The primary endpoint was overall response rate, and secondary endpoints included duration of response and safety. 

25 patients with R/R aggressive ATL (acute, lymphoma, or unfavorable chronic type), antibody-confirmed human T-lymphotropic virus type 1 (HTLV-1) infection, a median age of 69 years, and an average of 3 prior lines of therapy were enrolled in this study. ATL status consisted of 8 patients with relapsed ATL, 6 with recurrent, and 11 with refractory disease. All patients received valemetostat at 200 mg daily until disease progression or unacceptable toxicity occurred. 

Results indicated that the overall response rate was 48%, including 5 complete and 7b partial remissions. Patients who were pretreated with mogamulizumab (n=24) had an overall response rate of 45.8%, and patients with prior lenalidomide treatment (n=8) had an overall response rate of 50%. The duration of response was not reached. The median time to response was 1.4 months. 

Treatment-related adverse events were observed in all patients. The most common hematologic events were thrombocytopenia (80%), anemia (52%), neutropenia (28%), lymphopenia (24%), and leukopenia (20%). Serious adverse events occurred in 32% of patients (n=8), which led to treatment discontinuation in 1 patient. 

As endpoints were met, Dr Izutsu et al concluded, “valemetostat shows promise in treating relapsed, recurrent, or refractory ATL in patients with an extensive treatment history, including mogamulizumab.” They added, “The combination of clinical efficacy, antitumor properties, and an acceptable safety profile of valemetostat in our phase 2 study provides rationale for further investigation of this agent in ATL.”

Source: 

Izutsu K, Makita S, Nosaka K, et al. An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma. Blood. 2023; 141 (10): 1159–1168. doi: https://doi.org/10.1182/blood.2022016862