Complete response using the EZH2 inhibitor tazemetostat against multiple relapsed follicular lymphoma in the leukemic phase

Though multiple relapses and serial shortening of remission is one of the characteristics of follicular lymphoma (FL), standard third- and later-line treatments with clear evidence have not yet been established. Tazemetostat, the first oral enhancer of zester homolog 2 (EZH2) inhibitor, showed a favorable clinical outcome and safety profile against relapsed mutant EZH2 FL in a clinical trial and was applied to this clinical setting. Peripheral blood involvement, known as the leukemic phase, was observed in approximately 10% of patients with FL and reported as a poor prognostic factor. However, because of the infrequency of EZH2-activating mutations, clinical data on tazemetostat against FL in the leukemic phase is lacking. Herein, we report a case of multiple relapsed FL in the leukemic phase for which tazemetostat was administered as a sixth-line treatment. Tazemetostat monotherapy showed a slow and sustained clinical efficacy in the leukemic phase as shown by nodal involvement. Circulating lymphoma cells gradually decreased and disappeared in counts after 4 months of treatment. However, circulating lymphoma cells were still detected by flow cytometry up to 6 months of treatment and finally undetected after 9 months. Extended-interval dosing of tazemetostat transformed a partial response into a complete response. Thus, tazemetostat is effective for the treatment of multiple relapsed FL in the leukemic phase.