PMID- 29938772
OWN - NLM
STAT- MEDLINE
DCOM- 20190603
LR  - 20240328
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 182
IP  - 2
DP  - 2018 Jul
TI  - Twice-weekly ixazomib in combination with lenalidomide-dexamethasone in patients 
      with newly diagnosed multiple myeloma.
PG  - 231-244
LID - 10.1111/bjh.15394 [doi]
AB  - Weekly ixazomib with lenalidomide-dexamethasone (Rd) is feasible and has shown 
      activity in newly diagnosed multiple myeloma (NDMM) patients. This phase 1/2 
      study (NCT01383928) evaluated the recommended phase 2 dose (RP2D), 
      pharmacokinetics, safety and efficacy of twice-weekly ixazomib plus Rd in NDMM; 
      64 patients were enrolled across both phases. Patients received twice-weekly oral 
      ixazomib 3.0 or 3.7 mg plus lenalidomide 25 mg and dexamethasone 20 mg (10 mg in 
      cycles 9-16) for up to sixteen 21-day cycles, followed by maintenance with 
      twice-weekly ixazomib alone. No dose-limiting toxicities were reported in cycle 
      1; the RP2D was 3.0 mg based on overall tolerability across multiple cycles. In 
      62 evaluable patients, the confirmed overall response rate was 94% (68% >/=very 
      good partial response; 24% complete response). Median progression-free survival 
      was 24.9 months. Responses (median duration 36.9 months for patients receiving 
      the RP2D) deepened during treatment. Grade 3 drug-related adverse events (AEs) 
      occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%; 
      hyperglycaemia, 8%. There were no grade 4 drug-related AEs. Thirteen patients 
      discontinued due to AEs. Twice-weekly ixazomib-Rd offers substantial activity 
      with promising long-term outcomes in NDMM patients but may be associated with 
      greater toxicity compared with weekly ixazomib-Rd in this setting.
CI  - (c) 2018 The Authors. British Journal of Haematology published by John Wiley & Sons 
      Ltd and British Society for Haematology.
FAU - Richardson, Paul G
AU  - Richardson PG
AUID- ORCID: 0000-0002-7426-8865
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Hofmeister, Craig C
AU  - Hofmeister CC
AD  - Ohio State University, Columbus, OH, USA.
FAU - Rosenbaum, Cara A
AU  - Rosenbaum CA
AD  - Hematology/Oncology, University of Chicago Medicine, Chicago, IL, USA.
FAU - Htut, Myo
AU  - Htut M
AD  - Hematology and Stem Cell Transplant, City of Hope National Medical Center Duarte, 
      Duarte, CA, USA.
FAU - Vesole, David H
AU  - Vesole DH
AD  - John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, 
      USA.
FAU - Berdeja, Jesus G
AU  - Berdeja JG
AD  - Sarah Cannon Research Institute, Nashville, TN, USA.
FAU - Liedtke, Michaela
AU  - Liedtke M
AUID- ORCID: 0000-0001-8945-5850
AD  - Stanford Comprehensive Cancer Center, Stanford, CA, USA.
FAU - Chari, Ajai
AU  - Chari A
AD  - Mount Sinai School of Medicine Ruttenberg Treatment Center, New York, NY, USA.
FAU - Smith, Stephen D
AU  - Smith SD
AD  - Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, 
      USA.
FAU - Lebovic, Daniel
AU  - Lebovic D
AD  - University of Michigan Cancer Center, Ann Arbor, MI, USA.
FAU - Raje, Noopur
AU  - Raje N
AD  - Massachusetts General Hospital, Boston, MA, USA.
FAU - Byrne, Catriona
AU  - Byrne C
AD  - Millennium Pharmaceuticals Inc., Cambridge, MA, USA.
FAU - Liao, Eileen
AU  - Liao E
AD  - Millennium Pharmaceuticals Inc., Cambridge, MA, USA.
FAU - Gupta, Neeraj
AU  - Gupta N
AUID- ORCID: 0000-0002-5500-5218
AD  - Millennium Pharmaceuticals Inc., Cambridge, MA, USA.
FAU - Bacco, Alessandra Di
AU  - Bacco AD
AD  - Millennium Pharmaceuticals Inc., Cambridge, MA, USA.
FAU - Estevam, Jose
AU  - Estevam J
AD  - Millennium Pharmaceuticals Inc., Cambridge, MA, USA.
FAU - Berg, Deborah
AU  - Berg D
AD  - Millennium Pharmaceuticals Inc., Cambridge, MA, USA.
FAU - Baz, Rachid
AU  - Baz R
AD  - Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, 
      FL, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20180625
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Boron Compounds)
RN  - 71050168A2 (ixazomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - F0P408N6V4 (Lenalidomide)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Boron Compounds/administration & dosage/adverse effects/pharmacokinetics
MH  - Dexamethasone/administration & dosage/adverse effects/pharmacokinetics
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Glycine/administration & dosage/adverse effects/analogs & 
      derivatives/pharmacokinetics
MH  - Humans
MH  - Lenalidomide/administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
MH  - Treatment Outcome
PMC - PMC6055619
OTO - NOTNLM
OT  - ixazomib
OT  - multiple myeloma
OT  - newly diagnosed
OT  - oral
OT  - twice-weekly
EDAT- 2018/06/26 06:00
MHDA- 2019/06/04 06:00
PMCR- 2018/07/23
CRDT- 2018/06/26 06:00
PHST- 2018/01/12 00:00 [received]
PHST- 2018/03/19 00:00 [accepted]
PHST- 2018/06/26 06:00 [pubmed]
PHST- 2019/06/04 06:00 [medline]
PHST- 2018/06/26 06:00 [entrez]
PHST- 2018/07/23 00:00 [pmc-release]
AID - BJH15394 [pii]
AID - 10.1111/bjh.15394 [doi]
PST - ppublish
SO  - Br J Haematol. 2018 Jul;182(2):231-244. doi: 10.1111/bjh.15394. Epub 2018 Jun 25.