PMID- 32532790
OWN - NLM
STAT- MEDLINE
DCOM- 20211125
LR  - 20211125
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 26
IP  - 17
DP  - 2020 Sep 1
TI  - A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib 
      Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: 
      ECOG-ACRIN E2408.
PG  - 4468-4477
LID - 10.1158/1078-0432.CCR-20-1345 [doi]
AB  - PURPOSE: We sought to improve upon frontline bendamustine/rituximab (BR) 
      induction therapy followed by rituximab maintenance in untreated high-risk 
      follicular lymphoma (FL). PATIENTS AND METHODS: Patients were randomized to BR 
      induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and 
      rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with 
      rituximab maintenance (BR-LR). Dual primary objectives were complete remission 
      (CR) rate and 1-year disease-free survival (DFS); 289 patients enrolled 
      (NCT01216683). RESULTS: For induction, 92%, 87%, and 86% of patients randomized 
      to BR-R, BVR-R, or BR-LR received six cycles, respectively. CR rate with BR 
      versus BVR induction was 62% versus 75%, respectively (P = 0.04). One-year DFS 
      rates with BR-R versus BR-LR were 85% versus 67%, respectively (P = 0.0009). This 
      was due to an imbalance in CR rates post-BR induction and discontinuation due to 
      adverse events (AEs). The most common grade 3-4 AEs for BVR versus BR were 
      neutropenia and sensory neuropathy (12% vs <1%); 83% of the latter occurred with 
      intravenous bortezomib. The most common grade 3-4 AEs related to LR versus 
      rituximab maintenance were neutropenia 66% versus 21%, respectively (P < 0.0001), 
      and febrile neutropenia 10% versus 2%, respectively (P = 0.05). The overall 
      treatment-related mortality was 1.4%. With 5-year median follow-up, 3-year PFS 
      rates for BR-R, BVR-R, and BR-LR were 77%, 82%, and 76%, respectively (P = 0.36) 
      with OS rates of 87%, 90%, and 84%, respectively (P = 0.79). For prognostication, 
      CR rate and POD-24 were associated with survival. CONCLUSIONS: Altogether, 
      neither bortezomib added to BR induction nor lenalidomide added to rituximab 
      maintenance immediately post-BR induction is recommended in untreated FL.
CI  - (c)2020 American Association for Cancer Research.
FAU - Evens, Andrew M
AU  - Evens AM
AD  - Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. 
      ae378@cinj.rutgers.edu.
FAU - Hong, Fangxin
AU  - Hong F
AD  - Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, 
      Massachusetts.
FAU - Habermann, Thomas M
AU  - Habermann TM
AD  - Mayo Clinic, Rochester, Minnesota.
FAU - Advani, Ranjana H
AU  - Advani RH
AD  - Stanford Cancer Institute, Stanford, California.
FAU - Gascoyne, Randy D
AU  - Gascoyne RD
AD  - British Columbia Cancer Agency, Vancouver, Canada.
FAU - Witzig, Thomas E
AU  - Witzig TE
AUID- ORCID: 0000-0002-4215-6500
AD  - Mayo Clinic, Rochester, Minnesota.
FAU - Quon, Andrew
AU  - Quon A
AD  - University of California at Los Angeles, California.
FAU - Ranheim, Erik A
AU  - Ranheim EA
AD  - University of Wisconsin, Madison, Wisconsin.
FAU - Ansell, Stephen M
AU  - Ansell SM
AD  - Mayo Clinic, Rochester, Minnesota.
FAU - Cheema, Puneet Singh
AU  - Cheema PS
AD  - Saint John's Hospital Health East Care System, Maplewood, Minnesota.
FAU - Dy, Philip A
AU  - Dy PA
AD  - Decatur Memorial Hospital, Effingham, Illinois.
FAU - O'Brien, Timothy E
AU  - O'Brien TE
AD  - Case Western Reserve University, Cleveland, Ohio.
FAU - Winter, Jane N
AU  - Winter JN
AUID- ORCID: 0000-0001-7542-3305
AD  - Northwestern University, Chicago, Illinois.
FAU - Cescon, Terrence P
AU  - Cescon TP
AD  - Reading Hospital, West Reading, Pennsylvania.
FAU - Chang, Julie E
AU  - Chang JE
AD  - University of Wisconsin, Madison, Wisconsin.
FAU - Kahl, Brad S
AU  - Kahl BS
AD  - Washington University, St. Louis, Missouri.
LA  - eng
SI  - ClinicalTrials.gov/NCT01216683
GR  - UG1 CA233320/CA/NCI NIH HHS/United States
GR  - UG1 CA233234/CA/NCI NIH HHS/United States
GR  - UG1 CA232760/CA/NCI NIH HHS/United States
GR  - UG1 CA189830/CA/NCI NIH HHS/United States
GR  - UG1 CA189863/CA/NCI NIH HHS/United States
GR  - U10 CA180820/CA/NCI NIH HHS/United States
GR  - U10 CA180794/CA/NCI NIH HHS/United States
GR  - U10 CA180853/CA/NCI NIH HHS/United States
GR  - UG1 CA233339/CA/NCI NIH HHS/United States
GR  - UG1 CA233341/CA/NCI NIH HHS/United States
GR  - UG1 CA233277/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20200612
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 69G8BD63PP (Bortezomib)
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Bendamustine Hydrochloride/administration & dosage/adverse effects
MH  - Bortezomib/administration & dosage/adverse effects
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Lenalidomide/administration & dosage/adverse effects
MH  - Lymphoma, Follicular/*drug therapy/mortality
MH  - Maintenance Chemotherapy/adverse effects/methods
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*epidemiology/prevention & control
MH  - Progression-Free Survival
MH  - Remission Induction/methods
MH  - Rituximab/administration & dosage/adverse effects
MH  - Young Adult
PMC - PMC7722783
MID - NIHMS1604786
EDAT- 2020/06/14 06:00
MHDA- 2021/11/26 06:00
PMCR- 2021/03/01
CRDT- 2020/06/14 06:00
PHST- 2020/04/10 00:00 [received]
PHST- 2020/05/21 00:00 [revised]
PHST- 2020/06/09 00:00 [accepted]
PHST- 2020/06/14 06:00 [pubmed]
PHST- 2021/11/26 06:00 [medline]
PHST- 2020/06/14 06:00 [entrez]
PHST- 2021/03/01 00:00 [pmc-release]
AID - 1078-0432.CCR-20-1345 [pii]
AID - 10.1158/1078-0432.CCR-20-1345 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2020 Sep 1;26(17):4468-4477. doi: 10.1158/1078-0432.CCR-20-1345. 
      Epub 2020 Jun 12.