Titre :

A LYSA Phase Ib Study of tazemetostat (EPZ-6438) plus R-CHOP in newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) patients with poor prognosis features.

Auteur(s) :

Sarkozy, Clémentine [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Dubois, Sydney [Auteur]
Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel]
Molina, Thierry [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Michot, Jean Marie [Auteur]
Institut Gustave Roussy [IGR]
Cuillière-Dartigues, Peggy [Auteur]
Institut Gustave Roussy [IGR]
Suttle, Benjamin [Auteur]
North Carolina Central University [Durham]
Karlin, Lionel [Auteur]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Le Gouill, Steven [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Picquenot, Jean-Michel [Auteur]
Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel]
Dubois, Romain [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Tilly, Hervé [Auteur]
Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel]
Herbaux, Charles [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Jardin, Fabrice [Auteur]
Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel]
Salles, Gilles [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Ribrag, Vincent [Auteur]
Institut Gustave Roussy [IGR]

Titre de la revue :

Clinical Cancer Research

Nom court de la revue :

Clin. Cancer Res.

Numéro :

26

Pagination :

3145–3153

Éditeur :

American Association for Cancer Research

Date de publication :

2020-03-07

ISSN :

1078-0432

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Purpose: The histone-methyl transferase EZH2, catalytic subunit of the PRC2 complex involved in transcriptional regulation, is mutated in approximately 25% of germinal center B-cell lymphomas. Aberrant proliferative ...
Lire la suite >Purpose: The histone-methyl transferase EZH2, catalytic subunit of the PRC2 complex involved in transcriptional regulation, is mutated in approximately 25% of germinal center B-cell lymphomas. Aberrant proliferative dependency on EZH2 activity can be targeted by the orally available EZH2 inhibitor tazemetostat (EPZ-6438). We report the results of the phase Ib tazemetostat plus R-CHOP combination (NCT02889523), in patients 60 to 80 years of age with newly diagnosed diffuse large B-cell lymphoma. Patients and Methods: The primary objective of this dose-escalation study was to evaluate the safety of the combination and to determine the recommended phase II dose (RP2D) of tazemetostat. Results: A total of 17 patients were enrolled. During C1 and C2, two dose-limiting toxicities were observed: one grade 3 constipation at 400 mg and one grade 5 pulmonary infection at 800 mg. Grade 3 or more toxicities observed in more than 10% of the patients were constipation (24%), nausea (12%), and hypokalemia (12%). Grade 3 to 4 hematologic adverse events were recorded in 8 patients (47%): neutropenia (47%), leukopenia (29%), anemia (18%), and thrombocytopenia (12%). The tazemetostat RP2D was 800 mg. No organ-oriented toxicity increased with tazemetostat dosage escalation (severity and incidence). At 800 mg, AUC and Cmax of tazemetostat were similar compared with the single-agent study (E7438-G000-101). Conclusions: The RP2D of tazemetostat combined with R-CHOP is 800 mg twice a day. The association presents safety and PK comparable with R-CHOP alone. Preliminary efficacy data are encouraging and further investigations in phase II trial are warranted.Lire moins >

Langue :

Anglais

Audience :

Internationale

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Date de dépôt :

2023-05-25T03:39:15Z
2023-10-18T09:34:49Z