PMID- 31021005
OWN - NLM
STAT- MEDLINE
DCOM- 20200310
LR  - 20210109
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Print)
IS  - 0361-8609 (Linking)
VI  - 94
IP  - 7
DP  - 2019 Jul
TI  - Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory 
      multiple myeloma: A phase 1b study.
PG  - 794-802
LID - 10.1002/ajh.25498 [doi]
AB  - Twice-weekly carfilzomib (27 mg/m(2) ) with lenalidomide-dexamethasone (KRd) is a 
      standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b 
      study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received 
      carfilzomib (30-minute infusion; 56 or 70mg/m(2) ) on days 1, 8, and 15; 
      lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 
      (day 22 omitted for cycles 9+) of 28-day cycles. Primary objective was 
      safety/tolerability; efficacy was a secondary objective. Fifty-six RRMM patients 
      enrolled: 22 during dose evaluation (56-mg/m(2) , n = 10; 70-mg/m(2) , n = 12) 
      and 34 during dose expansion (all initiated dosing at 70 mg/m(2) ). After 2 fatal 
      adverse events (AEs) during 70-mg/m(2) dose expansion, dosage reduction to 
      56 mg/m(2) was permitted. Results are presented for carfilzomib 56-mg/m(2) (n = 
      10) and 70-mg/m(2) groups (dose evaluation/expansion; n = 46). Median carfilzomib 
      dose was 53.2 mg/m(2) (56-mg/m(2) group) and 62.4 mg/m(2) (70-mg/m(2) group). 
      Grade >/=3 AE rates were 70.0% (56 mg/m(2) ) and 69.6% (70 mg/m(2) ). Overall 
      response rates were 90.0% (56 mg/m(2) ) and 89.1% (70 mg/m(2) ); >/=very good 
      partial response rates were 50.0% (56 mg/m(2) ) and 73.9% (70 mg/m(2) ). 
      Once-weekly KRd was active with acceptable toxicity in RRMM, supporting further 
      evaluation of this regimen.
CI  - (c) 2019 The Authors. American Journal of Hematology published by Wiley 
      Periodicals, Inc.
FAU - Biran, Noa
AU  - Biran N
AUID- ORCID: 0000-0003-0693-4202
AD  - Myeloma Division, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, New Jersey.
FAU - Siegel, David
AU  - Siegel D
AD  - Myeloma Division, John Theurer Cancer Center, Hackensack University Medical 
      Center, Hackensack, New Jersey.
FAU - Berdeja, Jesus G
AU  - Berdeja JG
AD  - Department of Medicine, Sarah Cannon Research Institute, Nashville, Tennessee.
FAU - Raje, Noopur
AU  - Raje N
AD  - Department of Hematology and Oncology, Massachusetts General Hospital Cancer 
      Center, Boston, Massachusetts.
FAU - Cornell, Robert Frank
AU  - Cornell RF
AD  - Division of Hematology and Oncology, Vanderbilt University Medical Center, 
      Nashville, Tennessee.
FAU - Alsina, Melissa
AU  - Alsina M
AD  - Department of Blood and Marrow Transplantation, Moffit Cancer Center, Tampa, 
      Florida.
FAU - Kovacsovics, Tibor
AU  - Kovacsovics T
AD  - Division of Hematology and Hematologic Malignancies, Department of Internal 
      Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt 
      Lake City, Utah.
FAU - Fang, Belle
AU  - Fang B
AD  - Global Biostatistical Science, Amgen Inc., Thousand Oaks, California.
FAU - Kimball, Amy S
AU  - Kimball AS
AD  - Global Development, Amgen Inc., Thousand Oaks, California.
FAU - Landgren, Ola
AU  - Landgren O
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, 
      New York.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - Amgen, Inc./International
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190513
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (Oligopeptides)
RN  - 72X6E3J5AR (carfilzomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Dexamethasone/administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Lenalidomide/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/metabolism/pathology
MH  - Oligopeptides/administration & dosage/adverse effects
MH  - Recurrence
PMC - PMC6593978
COIS- Noa Biran: Honoraria and speakers' bureau participation for Celgene, Amgen, 
      Takeda, and Sanofi; consulting or advisory role fees and reimbursement of travel, 
      accommodations, or other expenses from Celgene, Amgen, and Takeda; and research 
      funding from Celgene and Amgen. David Siegel: Honoraria and consulting or 
      advisory role fees for Celgene, Amgen, Merck, Janssen, BMS, Takeda, and 
      Karyopharm; speakers' bureau participation for Celgene, Amgen, Merck, Janssen, 
      BMS, and Takeda; and research funding from Celgene. Jesus Berdeja: Research 
      funding from Abbvie, Amgen, Bluebird, BMS, Celgene, Genentech, Glenmark, Janssen, 
      Novartis, Poseida, Takeda, and Teva. Noopur Raje: Consulting or advisory role 
      fees for Amgen, Novartis, Takeda, Celgene, and Bluebird; and research funding 
      from AstraZeneca and Eli Lilly. R. Frank Cornell: Nothing to disclose. Melissa 
      Alsina: Honoraria from Janssen, Amgen, and Celgene; consulting or advisory role 
      fees for Celgene and BMS; speakers' bureau participation for Janssen and Amgen; 
      and research funding from BMS. Tibor Kovacsovics: Research support from Abbvie 
      and Amgen, and consulting fees from Amgen and Celgene. Belle Fang: Employed by 
      Amgen. Amy Kimball: Employed by Amgen; stock or other ownership with Amgen, and 
      stock ownership in WindMIL Therapeutics. Ola Landgren: Research funding from 
      National Institutes of Health, US Food and Drug Administration, Multiple Myeloma 
      Research Foundation, International Myeloma Foundation, Leukemia and Lymphoma 
      Society, Perelman Family Foundation, Rising Tides Foundation, Amgen, Celgene, 
      Janssen, Takeda, Glenmark, Seattle Genetics, and Karyopharm; has served on 
      honoraria/advisory boards for: Adaptive, Amgen, Binding Site, BMS, Celgene, 
      Cellectis, Glenmark, Janssen, Juno, Pfizer; and serves on Independent Data 
      Monitoring Committees for clinical trials led by Takeda, Merck, Janssen.
EDAT- 2019/04/26 06:00
MHDA- 2020/03/11 06:00
PMCR- 2019/06/26
CRDT- 2019/04/26 06:00
PHST- 2019/01/29 00:00 [received]
PHST- 2019/03/27 00:00 [revised]
PHST- 2019/04/22 00:00 [accepted]
PHST- 2019/04/26 06:00 [pubmed]
PHST- 2020/03/11 06:00 [medline]
PHST- 2019/04/26 06:00 [entrez]
PHST- 2019/06/26 00:00 [pmc-release]
AID - AJH25498 [pii]
AID - 10.1002/ajh.25498 [doi]
PST - ppublish
SO  - Am J Hematol. 2019 Jul;94(7):794-802. doi: 10.1002/ajh.25498. Epub 2019 May 13.