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

Cecilia Carpio, Reda Bouabdallah, Loïc Ysebaert, Juan Manuel Sancho, Gilles Salles, Raul Cordoba, Antonio Pinto, Mecide Gharibo, Drew Rasco, Carlos Panizo, Jose A. Lopez-Martin, Armando Santoro, Antonio Salar, Silvia Damian, Alejandro Martin, Gregor Verhoef, Eric Van den Neste, Maria Wang, Suzana Couto, Soraya CarrancioAndrew Weng, Xuehai Wang, Frank Schmitz, Xin Wei, Kristen Hege, Matthew W.B. Trotter, Alberto Risueño, Tonia J. Buchholz, Patrick R. Hagner, Anita K. Gandhi, Michael Pourdehnad, Vincent Ribrag

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)996-1007
Number of pages12
JournalBlood
Volume135
Issue number13
DOIs
Publication statusPublished - Mar 26 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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