PMID- 30068505
OWN - NLM
STAT- MEDLINE
DCOM- 20190723
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 132
IP  - 14
DP  - 2018 Oct 4
TI  - An open-label phase 1b study of obinutuzumab plus lenalidomide in 
      relapsed/refractory follicular B-cell lymphoma.
PG  - 1486-1494
LID - 10.1182/blood-2018-05-853499 [doi]
AB  - Obinutuzumab is a type II anti-CD20 monoclonal antibody that enhances 
      antibody-dependent cellular cytotoxicity better than rituximab. Given promising 
      results with lenalidomide and rituximab, this phase 1b study assessed the safety 
      and efficacy of lenalidomide combined with obinutuzumab (GALEN). Patients age >/=18 
      years with relapsed or refractory (R/R) follicular lymphoma (FL) after 
      rituximab-containing therapy received escalating doses (10 [n = 7], 15 [n = 3], 
      20 [n = 6], and 25 mg [n = 3]) of daily oral lenalidomide on days 1 to 21 of 
      cycle 1 and on days 2 to 22 of cycles 2 to 6 (28-day cycles). Obinutuzumab 1000 
      mg IV was administered on days 8, 15, and 22 (cycle 1) and on day 1 (cycles 2-6). 
      Dose was escalated in a 3 + 3 design based on dose-limiting toxicity (DLT) during 
      cycle 1 to establish the maximum tolerated dose (MTD). We observed 164 adverse 
      events (AEs), of which 139 were grade 1/2. The most common AEs were constipation 
      (52.6%), neutropenia (47.4%), and asthenia (36.8%); 64.3% (9 of 14) of the grade 
      3/4 AEs were neutropenia/neutrophil decrease, but without any febrile 
      neutropenia. Four DLTs occurred in 2 patients, all deemed unrelated to treatment. 
      MTD was not reached. Twelve patients (63.2%) responded: 8 complete, 3 unconfirmed 
      complete, and 1 partial response. Oral lenalidomide plus obinutuzumab is well 
      tolerated and effective in R/R FL. The recommended dose of lenalidomide was 
      established at 20 mg based on the risk of grade 3/4 neutropenia from cycle 2. 
      This trial was registered at www.clinicaltrials.gov as #NCT01582776.
CI  - (c) 2018 by The American Society of Hematology.
FAU - Morschhauser, Franck
AU  - Morschhauser F
AUID- ORCID: 0000-0002-3714-9824
AD  - Service des Maladies du Sang, Centre Hospitalier Regional Universitaire de Lille, 
      Groupe de Recherche sur les formes Injectables et les Technologies Associees, 
      Universite de Lille, Lille, France.
FAU - Salles, Gilles
AU  - Salles G
AD  - Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, University of 
      Lyon, Pierre-Benite, France.
FAU - Le Gouill, Steven
AU  - Le Gouill S
AD  - Department of Haematology, Centre Hospitalier Universitaire Nantes, Nantes, 
      France.
FAU - Tilly, Herve
AU  - Tilly H
AD  - Departement d'Hematologie, U1245, Centre Henri Becquerel, Universite de Rouen, 
      Rouen, France.
FAU - Thieblemont, Catherine
AU  - Thieblemont C
AD  - Hemato-Oncology Department, Assistance Publique-Hopitaux de Paris (AP-HP), INSERM 
      U728, Hospital Saint-Louis, Institut Universitaire d'Hematologie, Paris, France.
FAU - Bouabdallah, Krimo
AU  - Bouabdallah K
AD  - Service d'Hematologie et de Therapie Cellulaire, Centre Hospitalier Universitaire 
      Bordeaux, Bordeaux, France.
FAU - Fabiani, Bettina
AU  - Fabiani B
AD  - Hopital Saint-Antoine, AP-HP, Paris, France.
FAU - Menard, Cedric
AU  - Menard C
AD  - Unite Mixte de Recherche (UMR) S1236, INSERM, University of Rennes, Etablissement 
      Francais du Sang, Rennes, France.
AD  - Suivi Immunologique des Therapeutiques Innovantes, Centre Hospitalier 
      Universitaire de Rennes, Etablissement Francais du Sang, Rennes, France.
FAU - Tarte, Karin
AU  - Tarte K
AUID- ORCID: 0000-0002-6809-917X
AD  - Unite Mixte de Recherche (UMR) S1236, INSERM, University of Rennes, Etablissement 
      Francais du Sang, Rennes, France.
AD  - Suivi Immunologique des Therapeutiques Innovantes, Centre Hospitalier 
      Universitaire de Rennes, Etablissement Francais du Sang, Rennes, France.
FAU - Cartron, Guillaume
AU  - Cartron G
AD  - UMR 5235, Centre Hospitalier Universitaire, University of Montpellier, 
      Montpellier, France; and.
FAU - Houot, Roch
AU  - Houot R
AD  - Haematology Department, Centre Hospitalier Universitaire Rennes, Rennes, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT01582776
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20180801
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - F0P408N6V4 (Lenalidomide)
RN  - O43472U9X8 (obinutuzumab)
CIN - Blood. 2018 Oct 4;132(14):1465-1467. PMID: 30287467
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/administration & dosage/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Antineoplastic Agents, Immunological/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/therapeutic use
MH  - Female
MH  - Humans
MH  - Lenalidomide/administration & dosage/adverse effects/*therapeutic use
MH  - Lymphoma, B-Cell/*drug therapy
MH  - Lymphoma, Follicular/*drug therapy
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy
PMC - PMC6225348
COIS- Conflict-of-interest disclosure: F.M. has received personal fees for consultancy, 
      advisory boards, or scientific lectures from Gilead, Janssen, Celgene, Servier, 
      Bristol-Myers Squibb, Roche, and Epizyme (outside the submitted work); S.L.G. 
      received research grants, personal fees, and nonfinancial support from Celgene 
      and Roche Genentech during the conduct of the study and has received grants, 
      personal fees, and nonfinancial support from Celgene outside the submitted work; 
      H.T. has received research grants and personal fees from Celgene, personal fees 
      and nonfinancial support from Roche, and personal fees from Karyopharm, 
      AstraZeneca, and Bristol-Myers Squibb outside the submitted work; C.T. has 
      received consultancy fees or honoraria from Celgene, Bayer, AbbVie, and Janssen 
      and research funding from Roche; C.M. has received research funding from Celgene 
      and honoraria from Celgene and Bristol-Myers Squibb; K.T. has received research 
      funding from Celgene and honoraria from Celgene and Roche; G.C. has received 
      personal fees for consultancy and honoraria from Roche and Celgene and received 
      personal fees for honoraria from Sanofi, Gilead, and Janssen during the conduct 
      of the study; and R.H. has received consulting fees or honoraria from 
      Bristol-Myers Squibb and Gilead. The remaining authors declare no competing 
      financial interests.
EDAT- 2018/08/03 06:00
MHDA- 2019/07/25 06:00
PMCR- 2018/10/04
CRDT- 2018/08/03 06:00
PHST- 2018/05/23 00:00 [received]
PHST- 2018/07/19 00:00 [accepted]
PHST- 2018/08/03 06:00 [pubmed]
PHST- 2019/07/25 06:00 [medline]
PHST- 2018/08/03 06:00 [entrez]
PHST- 2018/10/04 00:00 [pmc-release]
AID - S0006-4971(20)60707-8 [pii]
AID - 2018/853499 [pii]
AID - 10.1182/blood-2018-05-853499 [doi]
PST - ppublish
SO  - Blood. 2018 Oct 4;132(14):1486-1494. doi: 10.1182/blood-2018-05-853499. Epub 2018 
      Aug 1.