TY - JOUR
T1 - Tazemetostat for patients with relapsed or refractory follicular lymphoma
T2 - an open-label, single-arm, multicentre, phase 2 trial
AU - Morschhauser, Franck
AU - Tilly, Hervé
AU - Chaidos, Aristeidis
AU - McKay, Pamela
AU - Phillips, Tycel
AU - Assouline, Sarit
AU - Batlevi, Connie Lee
AU - Campbell, Phillip
AU - Ribrag, Vincent
AU - Damaj, Gandhi Laurent
AU - Dickinson, Michael
AU - Jurczak, Wojciech
AU - Kazmierczak, Maciej
AU - Opat, Stephen
AU - Radford, John
AU - Schmitt, Anna
AU - Yang, Jay
AU - Whalen, Jennifer
AU - Agarwal, Shefali
AU - Adib, Deyaa
AU - Salles, Gilles
PY - 2020/11
Y1 - 2020/11
N2 - Background: Activating 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. Methods: This 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. Findings: Between 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. Interpretation: Tazemetostat 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. Funding: Epizyme.
AB - Background: Activating 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. Methods: This 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. Findings: Between 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. Interpretation: Tazemetostat 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. Funding: Epizyme.
UR - http://www.scopus.com/inward/record.url?scp=85094819055&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(20)30441-1
DO - 10.1016/S1470-2045(20)30441-1
M3 - Article
C2 - 33035457
AN - SCOPUS:85094819055
SN - 1470-2045
VL - 21
SP - 1433
EP - 1442
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 11
ER -