In patients with relapsed/refractory (R/R) adult T-cell leukemia/lymphoma (ATL), treatment with valemetostat tosilate (valemetostat) showed promising efficacy and safety in a phase 2 study based in Japan. The study investigators published their results in a report in the journal Blood.

Patients with R/R ATL have had limited options for treatment of this aggressive form of non-Hodgkin lymphoma, associated with T cells infected with human T-lymphotropic virus type 1 (HTLV-1). In Japan, ATL may account for 30% or more of all cases of T-cell lymphoma, according to the report. Among agents under study for treatment of R/R ATL is valemetostat, which is an inhibitor of both EZH1 and EZH2.

This phase 2 study ( Identifier: NCT04102150) enrolled patients in Japan with R/R ATL who were 20 years of age or older. Eligible patients included those having ATL diagnoses involving acute, lymphoma, or unfavorable chronic type, and also who had antibody-confirmed HTLV-1 infection. Valemetostat was given orally at a dose of 200 mg once daily and given as continuous treatment in 28-day cycles until progressive disease or unacceptable toxicity. Dose was adjusted for patients also receiving certain other therapies.

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The primary study endpoint was the overall response rate (ORR), assessed through independent central review, and several secondary endpoints were also evaluated. Efficacy and safety analyses included any patients who received at least 1 dose of valemetostat.

A total of 25 patients were included in analyses, and they had a median age of 69.0 years (range, 59-84) and a median of 3 prior lines of therapy (range, 1-8). Most patients had an Eastern Cooperative Oncology Group performance status of 0 (52.0%) or 1 (40.0%). Nearly all patients (96.0%) had received prior mogamulizumab therapy, most (96.0%) had received prior anthracycline-based therapy, and all (100.0%) had undergone prior hematopoietic stem cell transplantation.

The median study follow-up occurred at 6.5 months. In this study, the primary endpoint was met, with an ORR per central review of 48.0% (90% CI, 30.5%-65.9%; P <.0001). There were 5 patients who had complete remission and 7 with partial remission.

The ORR among patients who had prior mogamulizumab treatment was 45.8% (90% CI, 28.2%-64.2%), including 4 complete remissions and 7 partial remissions. Overall, the median duration of response was not reached. The median duration of treatment in this study was 4.3 months (range, 0.8-14.9).

The most common grade 3 or higher treatment-emergent adverse events (TEAEs) consisted of thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Serious TEAEs were seen in 8 patients, and there were reportedly 2 patients who discontinued treatment due to treatment-related adverse events.

There were no treatment-related deaths reported from this study. The investigators considered these safety findings indicative of a manageable and acceptable safety profile for valemetostat in this patient population.

“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,” the study investigators concluded in their report.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


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:10.1182/blood.2022016862