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The role of tazemetostat in relapsed/refractory follicular lymphoma.

ABSTRACT: Large strides have been made in the treatment of follicular lymphoma (FL) over the last few years. Although the majority of patients respond to upfront therapy, many experience disease progression with a progressive shortening of subsequent treatment free intervals. New treatment options are therefore crucial for such patients. Tazemetostat is a first-in-class, selective, oral inhibitor of enhancer of zester homolog 2 (EZH2), a histone methyltransferase that is mutated in about a quarter of FL cases. Tazemetostat was recently approved for the treatment of patients with relapsed FL after 2 or more prior lines of therapy in the presence of an EZH2 mutation and for those without any other available therapeutic option, independently of EZH2 mutation status. In this review, we will summarize the background and key data that led to the development of tazemetostat, and, ultimately, to its approval for this indication.

SUBMITTER: von Keudell G

PROVIDER: S-EPMC8165870 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The role of tazemetostat in relapsed/refractory follicular lymphoma.

von Keudell Gottfried G Salles Gilles G

Therapeutic advances in hematology 20210527

Large strides have been made in the treatment of follicular lymphoma (FL) over the last few years. Although the majority of patients respond to upfront therapy, many experience disease progression with a progressive shortening of subsequent treatment free intervals. New treatment options are therefore crucial for such patients. Tazemetostat is a first-in-class, selective, oral inhibitor of enhancer of zester homolog 2 (EZH2), a histone methyltransferase that is mutated in about a quarter of FL c ...[more]

PMID: 34104370

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Project description:BackgroundActivating mutations of EZH2, an epigenetic regulator, are present in approximately 20% of patients with follicular lymphoma. We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma.MethodsThis study was an open-label, single-arm, phase 2 trial done at 38 clinics or hospitals in France, the UK, Australia, Canada, Poland, Italy, Ukraine, Germany, and the USA. Eligible patients were adults (≥18 years) with histologically confirmed follicular lymphoma (grade 1, 2, 3a, or 3b) that had relapsed or was refractory to two or more systemic therapies, had an Eastern Cooperative Oncology Group performance status of 0-2, and had sufficient tumour tissue for central testing of EZH2 mutation status. Patients were categorised by EZH2 status: mutant (EZH2mut) or wild-type (EZH2WT). Patients received 800 mg of tazemetostat orally twice per day in continuous 28-day cycles. The primary endpoint was objective response rate based on the 2007 International Working Group criteria for non-Hodgkin lymphoma, assessed by an independent radiology committee. Activity and safety analyses were done in patients who received one dose or more of tazemetostat. This study is registered with ClinicalTrials.gov, NCT01897571, and follow-up is ongoing.FindingsBetween July 9, 2015, and May 24, 2019, 99 patients (45 in the EZH2mut cohort and 54 in the EZH2WT cohort) were enrolled in the study. At data cutoff for the analysis (Aug 9, 2019), the median follow-up was 22·0 months (IQR 12·0-26·7) for the EZH2mut cohort and 35·9 months (24·9-40·5) for the EZH2WT cohort. The objective response rate was 69% (95% CI 53-82; 31 of 45 patients) in the EZH2mut cohort and 35% (23-49; 19 of 54 patients) in the EZH2WT cohort. Median duration of response was 10·9 months (95% CI 7·2-not estimable [NE]) in the EZH2mut cohort and 13·0 months (5·6-NE) in the EZH2WT cohort; median progression-free survival was 13·8 months (10·7-22·0) and 11·1 months (3·7-14·6). Among all 99 patients, treatment-related grade 3 or worse adverse events included thrombocytopenia (three [3%]), neutropenia (three [3%]), and anaemia (two [2%]). Serious treatment-related adverse events were reported in four (4%) of 99 patients. There were no treatment-related deaths.InterpretationTazemetostat monotherapy showed clinically meaningful, durable responses and was generally well tolerated in heavily pretreated patients with relapsed or refractory follicular lymphoma. Tazemetostat is a novel treatment for patients with follicular lymphoma.FundingEpizyme.

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The role of tazemetostat in relapsed/refractory follicular lymphoma.

Publications

The role of tazemetostat in relapsed/refractory follicular lymphoma.

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