PMID- 31326409
OWN - NLM
STAT- MEDLINE
DCOM- 20200814
LR  - 20200814
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 19
IP  - 9
DP  - 2019 Sep
TI  - Oprozomib, pomalidomide, and Dexamethasone in Patients With Relapsed and/or 
      Refractory Multiple Myeloma.
PG  - 570-578.e1
LID - S2152-2650(19)30108-9 [pii]
LID - 10.1016/j.clml.2019.05.017 [doi]
AB  - INTRODUCTION: This phase Ib study evaluated oprozomib, an oral proteasome 
      inhibitor, plus pomalidomide-dexamethasone in relapsed/refractory multiple 
      myeloma (RRMM). PATIENTS AND METHODS: Patients received oprozomib once-daily on 
      days 1 to 5 and 15 to 19 (5/14 schedule; 150 mg/day starting dose) or on 2 
      consecutive days weekly (2/7 schedule; 210 mg/day starting dose) of 28-day 
      cycles, pomalidomide on days 1 to 21 (4 mg/day starting dose), and dexamethasone 
      20 mg on 2 consecutive days weekly. A 3 + 3 dose-escalation schema was used to 
      determine the maximum tolerated dose. RESULTS: Thirty-one patients were treated 
      (5/14, n = 4; 2/7, n = 27). Oprozomib maximum tolerated dose was not defined. The 
      2/7 schedule (oprozomib 210 mg/day, pomalidomide 4 mg/day) was selected for dose 
      expansion based on overall safety (n = 17). In this group, the most common 
      adverse events (AEs) were gastrointestinal (diarrhea [88.2%], nausea [58.8%], and 
      vomiting [58.8%]); grade >/= 3 gastrointestinal AEs were uncommon. The most common 
      grade >/= 3 AEs were hematologic (anemia [47.1%], neutropenia [35.3%], and 
      thrombocytopenia [29.4%]). One dose-limiting toxicity (gastric hemorrhage) 
      occurred; 3 patients discontinued owing to AEs. The overall response rate was 
      70.6%. CONCLUSION: Safety and pharmacokinetic profiles were concerns with the 
      oprozomib formulation used in this study and need to be improved. 
      Oprozomib-pomalidomide-dexamethasone (2/7 schedule) had encouraging efficacy, 
      supporting an ongoing phase Ib study evaluating new oprozomib formulations for 
      this combination in relapsed/refractory multiple myeloma.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Shah, Jatin
AU  - Shah J
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic 
      address: jatinshahmd@outlook.com.
FAU - Usmani, Saad
AU  - Usmani S
AD  - Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC. Electronic 
      address: Saad.Usmani@carolinashealthcare.org.
FAU - Stadtmauer, Edward A
AU  - Stadtmauer EA
AD  - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
FAU - Rifkin, Robert M
AU  - Rifkin RM
AD  - US Oncology Research and Rocky Mountain Cancer Centers, Denver, CO.
FAU - Berenson, James R
AU  - Berenson JR
AD  - Institute for Myeloma and Bone Cancer Research, West Hollywood, CA.
FAU - Berdeja, Jesus G
AU  - Berdeja JG
AD  - Sarah Cannon Research Institute, Nashville, TN.
FAU - Lyons, Roger M
AU  - Lyons RM
AD  - US Oncology Research and Texas Oncology, San Antonio, TX.
FAU - Klippel, Zandra
AU  - Klippel Z
AD  - Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA.
FAU - Chang, Yu-Lin
AU  - Chang YL
AD  - Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA.
FAU - Niesvizky, Ruben
AU  - Niesvizky R
AD  - Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190529
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (ONX 0912)
RN  - 0 (Oligopeptides)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - D2UX06XLB5 (pomalidomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Dexamethasone/administration & dosage/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/diagnosis/*drug therapy/mortality
MH  - Neoplasm Recurrence, Local
MH  - Neoplasm Staging
MH  - Oligopeptides/administration & dosage/pharmacokinetics
MH  - Research Design
MH  - Retreatment
MH  - Thalidomide/administration & dosage/analogs & derivatives/pharmacokinetics
OTO - NOTNLM
OT  - Clinical trials
OT  - Oncology
OT  - Pharmacokinetics
OT  - Proteasome inhibitor
OT  - Therapy
EDAT- 2019/07/22 06:00
MHDA- 2020/08/15 06:00
CRDT- 2019/07/22 06:00
PHST- 2019/01/31 00:00 [received]
PHST- 2019/04/25 00:00 [revised]
PHST- 2019/05/26 00:00 [accepted]
PHST- 2019/07/22 06:00 [pubmed]
PHST- 2020/08/15 06:00 [medline]
PHST- 2019/07/22 06:00 [entrez]
AID - S2152-2650(19)30108-9 [pii]
AID - 10.1016/j.clml.2019.05.017 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2019 Sep;19(9):570-578.e1. doi: 
      10.1016/j.clml.2019.05.017. Epub 2019 May 29.