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Blood. 2020 Jan 23. pii: blood.2019002395. doi: 10.1182/blood.2019002395. [Epub ahead of print]

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

Author information

1
Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, University Autònoma of Barcelona (UAB), Barcelona, Spain, Barcelona, Spain.
2
Institut Paoli-Calmettes, Marseille, France.
3
Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
4
ICO-Hospital Germans Trias i Pujol. Universitat Autonoma de Barcelona, Badalona, Spain.
5
Hospices Civils de Lyon, Pierre Benite, France.
6
Fundación Jimenez Díaz University Hospital, Madrid, Spain.
7
National Cancer Institute, Fondazione Pascale, IRCCS, Naples, Italy.
8
Bristol-Myers Squibb, Summit, New Jersey, United States.
9
South Texas Accelerated Research Therapeutics, San Antonio, Texas, United States.
10
Clinica Universidad de Navarra, Pamplona, Spain.
11
12 de Octubre University Hospital & Research Institute, GETICA, Madrid, Spain.
12
Humanitas Cancer Center, Rozzano, Italy.
13
HOSPITAL DEL MAR, BARCELONA, Spain.
14
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
15
Hospital Universitario de Salamanca, Salamanca, Spain.
16
University Hospitals K.U.Leuven.
17
Cliniques universitaires Saint-Luc, Brussels, Belgium.
18
Bristol-Myers Squibb, San Diego, California, United States.
19
Genmab, LA JOLLA, California, United States.
20
BC Cancer Agency, Vancouver, British Columbia, Canada.
21
BCCRC, Vancouver, Canada.
22
Fred Hutch, Seattle, Washington, United States.
23
Bristol-Myers Squibb, Berkeley Heights, New Jersey, United States.
24
Bristol Myers Squibb, San Francisco, California, United States.
25
Celgene Institute for Translational Research Europe, A Bristol-Myers Squibb Company, Sevilla, Spain.
26
Celgene Institute for Translational Research Europe, A Bristol-Myers Squibb Company, Seville, Spain.
27
Bristol-Myers Squibb, San Francisco, California, United States.
28
Bristol-Meyers Squibb, San Francisco, California, United States.
29
Institut Gustave-Roussy, Villejuif, France.

Abstract

Treatment options for relapsed/refractory diffuse large B-cell lymphoma (R/R 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 R/R de novo 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 transformed lymphoma, received 3 to 5 mg of 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 versus 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.

PMID:
31977002
DOI:
10.1182/blood.2019002395

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