Avadomide monotherapy in relapsed/refractory DLBCL: safety, efficacy, and a predictive gene classifier.

Autor:	Carpio C; Department of Hematology, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, Universitat Autònoma of Barcelona, Barcelona, Spain., Bouabdallah R; Institut Paoli-Calmettes, Marseille, France., Ysebaert L; Centre Hospitalier Universitaire de Toulouse, Toulouse, France., Sancho JM; Catalan Institute of Oncology (ICO)-Josep Carreras Leukaemia Research Institute (IJC)-Hospital Universitari Germans Trias i Pujol, Badalona, Spain., Salles G; Centre Hospitalier Lyon-Sud, Pierre-Bénite, France., Cordoba R; Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain., Pinto A; Istituto Nazionale Tumori, Fondazione G. Pascale, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Napoli, Italy., Gharibo M; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ., Rasco D; South Texas Accelerated Research Therapeutics LLC, San Antonio, TX., Panizo C; Clinica Universidad de Navarra, Pamplona, Spain., Lopez-Martin JA; 12 de Octubre University Hospital & Research Institute, Grupo Español de Terapias Inmuno-Biológicas en Cáncer (GÉTICA), Madrid, Spain., Santoro A; Humanitas Research Hospital and Cancer Center, Milan, Rozzano, Italy., Salar A; Hospital del Mar, Barcelona, Spain., Damian S; Fondazione IRCCS, Milan, Italy., Martin A; Hospital Universitario de Salamanca and Instituto de Investigación Biomedica de Salamanca (IBSAL), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Salamanca, Spain., Verhoef G; UZ Gasthuisberg Leuven, Leuven, Belgium., Van den Neste E; Cliniques Universitaires Saint-Luc, Université de Louvain, Brussels, Belgium., Wang M; Bristol-Myers Squibb, San Diego, CA., Couto S; Genmab Pharmaceuticals, Princeton, NJ., Carrancio S; Bristol-Myers Squibb, San Diego, CA., Weng A; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada., Wang X; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada., Schmitz F; Fred Hutchinson Cancer Research Center, Seattle, WA., Wei X; Bristol-Myers Squibb, Berkeley Heights, NJ., Hege K; Bristol-Myers Squibb, San Francisco, CA., Trotter MWB; Celgene Institute for Translational Research Europe, A Bristol-Myers Squibb Company, Seville, Spain., Risueño A; Celgene Institute for Translational Research Europe, A Bristol-Myers Squibb Company, Seville, Spain., Buchholz TJ; Bristol-Myers Squibb, San Francisco, CA., Hagner PR; Bristol-Myers Squibb, Summit, NJ; and., Gandhi AK; Bristol-Myers Squibb, Summit, NJ; and., Pourdehnad M; Bristol-Myers Squibb, San Francisco, CA., Ribrag V; Institut Gustave Roussy, Villejuif, France.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2020 Mar 26; Vol. 135 (13), pp. 996-1007.
DOI:	10.1182/blood.2019002395
Abstrakt:	Treatment options for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are limited, with no standard of care; prognosis is poor, with 4- to 6-month median survival. Avadomide (CC-122) is a cereblon-modulating agent with immunomodulatory and direct antitumor activities. This phase 1 dose-expansion study assessed safety and clinical activity of avadomide monotherapy in patients with de novo R/R DLBCL and transformed lymphoma. Additionally, a novel gene expression classifier, which identifies tumors with a high immune cell infiltration, was shown to enrich for response to avadomide in R/R DLBCL. Ninety-seven patients with R/R DLBCL, including 12 patients with transformed lymphoma, received 3 to 5 mg avadomide administered on continuous or intermittent schedules until unacceptable toxicity, disease progression, or withdrawal. Eighty-two patients (85%) experienced ≥1 grade 3/4 treatment-emergent adverse events (AEs), most commonly neutropenia (51%), infections (24%), anemia (12%), and febrile neutropenia (10%). Discontinuations because of AEs occurred in 10% of patients. Introduction of an intermittent 5/7-day schedule improved tolerability and reduced frequency and severity of neutropenia, febrile neutropenia, and infections. Among 84 patients with de novo R/R DLBCL, overall response rate (ORR) was 29%, including 11% complete response (CR). Responses were cell-of-origin independent. Classifier-positive DLBCL patients (de novo) had an ORR of 44%, median progression-free survival (mPFS) of 6 months, and 16% CR vs an ORR of 19%, mPFS of 1.5 months, and 5% CR in classifier-negative patients (P = .0096). Avadomide is being evaluated in combination with other antilymphoma agents. This trial was registered at www.clinicaltrials.gov as #NCT01421524. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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