PMID- 31977002
OWN - NLM
STAT- MEDLINE
DCOM- 20201020
LR  - 20210910
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 135
IP  - 13
DP  - 2020 Mar 26
TI  - Avadomide monotherapy in relapsed/refractory DLBCL: safety, efficacy, and a 
      predictive gene classifier.
PG  - 996-1007
LID - 10.1182/blood.2019002395 [doi]
AB  - 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.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Carpio, Cecilia
AU  - Carpio C
AD  - Department of Hematology, Vall d'Hebron Institute of Oncology, University 
      Hospital Vall d'Hebron, Universitat Autonoma of Barcelona, Barcelona, Spain.
FAU - Bouabdallah, Reda
AU  - Bouabdallah R
AD  - Institut Paoli-Calmettes, Marseille, France.
FAU - Ysebaert, Loic
AU  - Ysebaert L
AD  - Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
FAU - Sancho, Juan-Manuel
AU  - Sancho JM
AD  - Catalan Institute of Oncology (ICO)-Josep Carreras Leukaemia Research Institute 
      (IJC)-Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
FAU - Salles, Gilles
AU  - Salles G
AD  - Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
FAU - Cordoba, Raul
AU  - Cordoba R
AD  - Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain.
FAU - Pinto, Antonio
AU  - Pinto A
AD  - Istituto Nazionale Tumori, Fondazione G. Pascale, Istituto di Ricovero e Cura a 
      Carattere Scientifico (IRCCS), Napoli, Italy.
FAU - Gharibo, Mecide
AU  - Gharibo M
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.
FAU - Rasco, Drew
AU  - Rasco D
AD  - South Texas Accelerated Research Therapeutics LLC, San Antonio, TX.
FAU - Panizo, Carlos
AU  - Panizo C
AD  - Clinica Universidad de Navarra, Pamplona, Spain.
FAU - Lopez-Martin, Jose A
AU  - Lopez-Martin JA
AD  - 12 de Octubre University Hospital & Research Institute, Grupo Espanol de Terapias 
      Inmuno-Biologicas en Cancer (GETICA), Madrid, Spain.
FAU - Santoro, Armando
AU  - Santoro A
AD  - Humanitas Research Hospital and Cancer Center, Milan, Rozzano, Italy.
FAU - Salar, Antonio
AU  - Salar A
AD  - Hospital del Mar, Barcelona, Spain.
FAU - Damian, Silvia
AU  - Damian S
AD  - Fondazione IRCCS, Milan, Italy.
FAU - Martin, Alejandro
AU  - Martin A
AD  - Hospital Universitario de Salamanca and Instituto de Investigacion Biomedica de 
      Salamanca (IBSAL), Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), 
      Salamanca, Spain.
FAU - Verhoef, Gregor
AU  - Verhoef G
AD  - UZ Gasthuisberg Leuven, Leuven, Belgium.
FAU - Van den Neste, Eric
AU  - Van den Neste E
AD  - Cliniques Universitaires Saint-Luc, Universite de Louvain, Brussels, Belgium.
FAU - Wang, Maria
AU  - Wang M
AD  - Bristol-Myers Squibb, San Diego, CA.
FAU - Couto, Suzana
AU  - Couto S
AD  - Genmab Pharmaceuticals, Princeton, NJ.
FAU - Carrancio, Soraya
AU  - Carrancio S
AD  - Bristol-Myers Squibb, San Diego, CA.
FAU - Weng, Andrew
AU  - Weng A
AD  - Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
FAU - Wang, Xuehai
AU  - Wang X
AD  - Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
FAU - Schmitz, Frank
AU  - Schmitz F
AD  - Fred Hutchinson Cancer Research Center, Seattle, WA.
FAU - Wei, Xin
AU  - Wei X
AD  - Bristol-Myers Squibb, Berkeley Heights, NJ.
FAU - Hege, Kristen
AU  - Hege K
AD  - Bristol-Myers Squibb, San Francisco, CA.
FAU - Trotter, Matthew W B
AU  - Trotter MWB
AD  - Celgene Institute for Translational Research Europe, A Bristol-Myers Squibb 
      Company, Seville, Spain.
FAU - Risueno, Alberto
AU  - Risueno A
AD  - Celgene Institute for Translational Research Europe, A Bristol-Myers Squibb 
      Company, Seville, Spain.
FAU - Buchholz, Tonia J
AU  - Buchholz TJ
AD  - Bristol-Myers Squibb, San Francisco, CA.
FAU - Hagner, Patrick R
AU  - Hagner PR
AD  - Bristol-Myers Squibb, Summit, NJ; and.
FAU - Gandhi, Anita K
AU  - Gandhi AK
AD  - Bristol-Myers Squibb, Summit, NJ; and.
FAU - Pourdehnad, Michael
AU  - Pourdehnad M
AD  - Bristol-Myers Squibb, San Francisco, CA.
FAU - Ribrag, Vincent
AU  - Ribrag V
AD  - Institut Gustave Roussy, Villejuif, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT01421524
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Piperidones)
RN  - 0 (Quinazolinones)
SB  - IM
EIN - Blood. 2021 Apr 15;137(15):2126. PMID: 33856449
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Biomarkers
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Immunophenotyping
MH  - Lymphoma, Large B-Cell, Diffuse/*drug therapy/genetics/mortality/*pathology
MH  - Macrophages/immunology/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Odds Ratio
MH  - Piperidones/administration & dosage/adverse effects/pharmacokinetics/*therapeutic 
      use
MH  - Prognosis
MH  - Quinazolinones/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Recurrence
MH  - Retreatment
MH  - T-Lymphocytes/immunology/metabolism
MH  - Treatment Outcome
PMC - PMC7099331
COIS- Conflict-of-interest disclosure: C.C. received travel grants from Takeda, 
      Janssen, Roche, and Celgene, A Bristol-Myers Squibb Company. L.Y. reports 
      research funding from Janssen and Roche, and served on the advisory board for 
      Abbvie, Gilead, Roche, and Janssen. J.-M.S. received travel grants from Roche and 
      honoraria from Roche, Gilead, Janssen, Celgene, A Bristol-Myers Squibb Company, 
      Kern-Pharma and Servier and served on the advisory board of Roche, Gilead, 
      Janssen, Bristol-Myers Squibb, Kern-Pharma, and Celltrion. G.S. received research 
      funding from Roche and Celgene, A Bristol-Myers Squibb Company, and served on the 
      advisory board for Novartis. R.C. participated in a speaker's bureau for Roche, 
      Janssen, and Celgene, A Bristol-Myers Squibb Company; received honoraria from 
      Roche, Janssen, and Celgene, A Bristol-Myers Squibb Company; served on the 
      advisory board for Janssen, Celgene, A Bristol-Myers Squibb Company, and Servier; 
      and received travel grants from Roche, Janssen, Celgene, A Bristol-Myers Squibb 
      Company, AbbVie, and Pfizer. A.P. participated in a speaker's bureau for Roche; 
      received patents or royalties from EDO-Mundipharma; received honoraria from 
      Roche, MSD, Bristol-Myers Squibb, and Servier; served on the advisory board of 
      Servier, Roche, Bristol-Myers Squibb, and MSD; and received travel grants from 
      Roche and Takeda. D.R. served on the advisory board of Boehringer Ingelheim and 
      Eli Lilly, received travel grants from Asana, and received research funding from 
      Celgene, A Bristol-Myers Squibb Company. C.P. participated in a speaker's bureau 
      for Roche and Janssen, served on the advisory board of Bristol-Myers Squibb and 
      Kyowa Kirin, and received travel grants from Roche. J.A.L.-M. participated in a 
      speaker's bureau for Bristol-Myers Squibb, Roche, and MSD; received patents or 
      royalties and reports equity ownership from PharmaMar; received travel grants 
      from Bristol Myers-Squibb, Roche, and MSD; and received research funding from 
      Iovance, Adaptimmune, Novartis, Roche, Merck, Pfizer, MSD, and Celgene, A 
      Bristol-Myers Squibb Company. A. Santoro participated in a speaker's bureau for 
      Takeda, Roche, AbbVie, Amgen, Celgene, A Bristol-Myers Squibb Company, 
      AstraZeneca, Eli Lilly, Sandoz, and Novartis and served on the advisory board for 
      Bristol-Myers Squibb, Servier, Gilead, Pfizer, Eisai, Arqule, Bayer, and MSD. A. 
      Salar participated in a speaker's bureau for Roche and Janssen; received travel 
      grants from Roche; served on the advisory board of Celgene, A Bristol-Myers 
      Squibb Company, Roche, Janssen, Gilead; and reports research funding from Roche 
      and Gilead. S.D. reports research funding from Novartis. A.M. received honoraria 
      from Celgene, A Bristol-Myers Squibb Company, Roche, Janssen, and Servier; served 
      on the advisory board of Roche, Celgene, A Bristol-Myers Squibb Company, and 
      MorPhosys; provided expert testimony on behalf of Gilead; received travel grants 
      from Roche, Celgene, A Bristol-Myers Squibb Company, Janssen, Servier, and 
      Mundipharma; and reports research funding from Celgene, A Bristol-Myers Squibb 
      Company, Janssen, Teva, and Mundipharma. A.W. received patents and royalties from 
      BC Cancer Agency, received travel grants from Dava Oncology, served on the 
      advisory board for m-panels and Guidepoint global, and reports research funding 
      from Celgene, A Bristol-Myers Squibb Company. T.J.B. has equity ownership with 
      Amgen. V.R. received honoraria from Infinity Pharmaceuticals, Bristol-Myers 
      Squibb, Eisai, PharmaMar, and Gilead Sciences; served on the advisory board for 
      Infinity Pharmaceuticals, Bristol-Myers Squibb, PharmaMar, Gilead Sciences, 
      NanoString Technologies, Incyte, MSD, Roche, Genentech, and Epizyme; provided 
      expert testimony on behalf of Servier, reports research funding from arGEN-X 
      BVBA; and received travel grants from Roche and Bristol-Myers Squibb. F.S. has 
      equity ownership with Bristol-Myers Squibb. S. Couto had equity ownership with 
      Celgne, A Bristol-Myers Squibb Company. M.G., S. Carrancio, X. Wei, K.H., 
      M.W.B.T., A.R., M.W., T.J.B., P.R.H., A.K.G., and M.P. are employees of 
      Bristol-Myers Squibb and have equity ownership with Bristol-Myers Squibb. R.B., 
      G.V., E.V.d.N., and X. Wang declare no competing financial interests.
EDAT- 2020/01/25 06:00
MHDA- 2020/10/21 06:00
PMCR- 2020/03/26
CRDT- 2020/01/25 06:00
PHST- 2019/07/18 00:00 [received]
PHST- 2020/01/08 00:00 [accepted]
PHST- 2020/01/25 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/01/25 06:00 [entrez]
PHST- 2020/03/26 00:00 [pmc-release]
AID - S0006-4971(20)62151-6 [pii]
AID - 2020/BLD2019002395 [pii]
AID - 10.1182/blood.2019002395 [doi]
PST - ppublish
SO  - Blood. 2020 Mar 26;135(13):996-1007. doi: 10.1182/blood.2019002395.