Phase I Study of EZH2 Inhibitor Tulmimetostat in Cutaneous T-cell Lymphoma

Blood Cancer
Neha Metha-Shah, MD, MSCI
Washington University School of Medicine


Cutaneous T-cell lymphomas (CTCL) are a rare subset of T-cell non-Hodgkin’s lymphomas that are present in the skin but can also involve the lymph nodes and bloodstream. Mycosis fungoides (MF) and its rarer leukemic variant, Sezary syndrome (SS), represent architypes of CTCL. There are approximately 2,000 new cases of CTCL diagnosed every year in the US. ​Due to the rare nature of this disease and limited number of expert centers, there are few clinical studies devoted to this disease. Patients who present with advanced-stage MF have an estimated 5-year survival of 20%. ​Current treatment has limited response rates and is limited by cumulative toxicity. Given the relatively meager response rates and the toxicity profile of these treatments, better-tolerated therapies for this rare disease are needed. ​Genetic alterations and overexpression of EZH2 are common in many cancers. Drugs targeting EZH2 have been found to be effective in several types of lymphomas including acute T-cell leukemia/lymphoma involving the skin. In addition, they can be taken orally and have a limited toxicity profile. ​Given the promising activity tulmimetostat, a new, second-generation EZH2 targeting agent, in T-cell lymphoma involving the skin and the excellent tolerability of the agent, the researchers are proposing a phase I trial assessing the safety tulmimetostat in patients with advanced MF and SS. ​This study will be the first clinical use of EZH2 inhibitors in CTCL. They will also use a novel quality of life tool specific to CTCL developed by the group

Trial Registration: Identifier: NCT05944562