PMID- 26384354
OWN - NLM
STAT- MEDLINE
DCOM- 20160222
LR  - 20220410
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 126
IP  - 20
DP  - 2015 Nov 12
TI  - Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma.
PG  - 2284-90
LID - 10.1182/blood-2015-05-643320 [doi]
AB  - Treatment options for patients with heavily pretreated relapsed and/or refractory 
      multiple myeloma remain limited. We evaluated a novel therapeutic regimen 
      consisting of carfilzomib, pomalidomide, and dexamethasone (CPD) in an 
      open-label, multicenter, phase 1, dose-escalation study. Patients who relapsed 
      after prior therapy or were refractory to the most recently received therapy were 
      eligible. All patients were refractory to prior lenalidomide. Patients received 
      carfilzomib IV on days 1, 2, 8, 9, 15, and 16 (starting dose of 20/27 mg/m(2)), 
      pomalidomide once daily on days 1 to 21 (4 mg as the initial dose level), and 
      dexamethasone (40 mg oral or IV) on days 1, 8, 15, and 22 of 28-day cycles. The 
      primary objective was to evaluate the safety and determine the maximum tolerated 
      dose (MTD) of the regimen. A total of 32 patients were enrolled. The MTD of the 
      regimen was dose level 1 (carfilzomib 20/27 mg/m(2), pomalidomide 4 mg, 
      dexamethasone 40 mg). Hematologic adverse events (AEs) occurred in >/=60% of all 
      patients, including 11 patients with grade >/=3 anemia. Dyspnea was limited to 
      grade 1/2 in 10 patients. Peripheral neuropathy was uncommon and limited to grade 
      1/2. Eight patients had dose reductions during therapy, and 7 patients 
      discontinued treatment due to AEs. Two deaths were noted on study due to 
      pneumonia and pulmonary embolism (n = 1 each). The combination of CPD is 
      well-tolerated and highly active in patients with relapsed/refractory multiple 
      myeloma. This trial was registered at www.clinicaltrials.gov as #NCT01464034.
CI  - (c) 2015 by The American Society of Hematology.
FAU - Shah, Jatin J
AU  - Shah JJ
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX;
FAU - Stadtmauer, Edward A
AU  - Stadtmauer EA
AD  - Clinical Research Unit, University of Pennsylvania Abramson Cancer Center, 
      Philadelphia, PA;
FAU - Abonour, Rafat
AU  - Abonour R
AD  - Indiana University Simon Cancer Center, Indianapolis, IN;
FAU - Cohen, Adam D
AU  - Cohen AD
AD  - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA;
FAU - Bensinger, William I
AU  - Bensinger WI
AD  - Clinical Research Division, Fred Hutchinson Cancer Center Research Center, 
      Seattle, WA;
FAU - Gasparetto, Cristina
AU  - Gasparetto C
AD  - Division of Hematological Malignancies and Cellular Therapy, Department of 
      Medicine, Duke University Medical Center, Durham, NC;
FAU - Kaufman, Jonathan L
AU  - Kaufman JL
AD  - Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute, Emory 
      University, Atlanta, GA;
FAU - Lentzsch, Suzanne
AU  - Lentzsch S
AD  - Division of Hematology/Oncology, Department of Medicine, Colombia University 
      Medical Center, New York, NY;
FAU - Vogl, Dan T
AU  - Vogl DT
AD  - Clinical Research Unit, University of Pennsylvania Abramson Cancer Center, 
      Philadelphia, PA;
FAU - Gomes, Christina L
AU  - Gomes CL
AD  - Criterium, Inc-Academic Myeloma Consortium, Saratoga Springs, NY;
FAU - Pascucci, Natalia
AU  - Pascucci N
AD  - Criterium, Inc-Academic Myeloma Consortium, Saratoga Springs, NY;
FAU - Smith, David D
AU  - Smith DD
AD  - Division of Biostatistics, Department of Information Sciences, City of Hope, 
      Duarte, CA; and.
FAU - Orlowski, Robert Z
AU  - Orlowski RZ
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, Houston, TX;
FAU - Durie, Brian G M
AU  - Durie BG
AD  - Cedars Sinai Samuel Oschin Cancer Center, Los Angeles, CA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01464034
GR  - P50 CA142509/CA/NCI NIH HHS/United States
GR  - R01 CA184464/CA/NCI NIH HHS/United States
GR  - U10 CA032102/CA/NCI NIH HHS/United States
GR  - UL1 TR000371/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150917
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Oligopeptides)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 72X6E3J5AR (carfilzomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - D2UX06XLB5 (pomalidomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Dexamethasone/administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/mortality/pathology
MH  - Oligopeptides/administration & dosage/adverse effects
MH  - Pneumonia/chemically induced/mortality
MH  - Pulmonary Embolism/chemically induced/mortality
MH  - Recurrence
MH  - Thalidomide/administration & dosage/adverse effects/analogs & derivatives
MH  - Time Factors
PMC - PMC4643003
EDAT- 2015/09/19 06:00
MHDA- 2016/02/24 06:00
PMCR- 2015/11/12
CRDT- 2015/09/19 06:00
PHST- 2015/05/04 00:00 [received]
PHST- 2015/09/08 00:00 [accepted]
PHST- 2015/09/19 06:00 [entrez]
PHST- 2015/09/19 06:00 [pubmed]
PHST- 2016/02/24 06:00 [medline]
PHST- 2015/11/12 00:00 [pmc-release]
AID - S0006-4971(20)30737-0 [pii]
AID - 2015/643320 [pii]
AID - 10.1182/blood-2015-05-643320 [doi]
PST - ppublish
SO  - Blood. 2015 Nov 12;126(20):2284-90. doi: 10.1182/blood-2015-05-643320. Epub 2015 
      Sep 17.