PMID- 35417741
OWN - NLM
STAT- MEDLINE
DCOM- 20220621
LR  - 20221006
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 111
DP  - 2022 Jul
TI  - A phase 1/2 study of ixazomib in place of bortezomib or carfilzomib in a 
      subsequent line of therapy for patients with multiple myeloma refractory to their 
      last bortezomib or carfilzomib combination regimen.
PG  - 79-86
LID - S0301-472X(22)00157-6 [pii]
LID - 10.1016/j.exphem.2022.04.003 [doi]
AB  - Identifying effective combination regimens is a high priority in multiple myeloma 
      (MM), as most patients eventually become refractory to their current treatments. 
      In this study, we investigated whether the proteasome inhibitor (PI) ixazomib 
      could delay disease progression among patients who failed regimens containing 
      another PI, bortezomib or carfilzomib. This phase 1/2, multicenter, open-label, 
      nonrandomized study enrolled patients who were refractory to a previous regimen 
      containing bortezomib or carfilzomib. Patients continued the other anti-MM drugs 
      in the regimen at the same doses and frequencies. Patients with combination 
      regimens with unknown maximum tolerated dose (MTD) of ixazomib were enrolled in 
      phase 1, with ixazomib starting at 3 mg and then dose escalated to 4 mg. Patients 
      on regimens with a known ixazomib MTD were enrolled in phase 2. Primary endpoints 
      were overall response rate (ORR), clinical benefit rate (CBR), adverse events 
      (AEs), and determination of maximum tolerated dose (MTD). Of the 46 patients 
      enrolled, 39 were evaluable for efficacy. ORR and CBR were 12.8% and 17.9%, 
      respectively. Ixazomib appeared to be well tolerated as a replacement for 
      carfilzomib and bortezomib, with 23.9% of patients experiencing at least one 
      grade >/=3 serious adverse event (SAE) and 37.0% experiencing at least one grade >/=3 
      AE. The most common grade >/=3 AEs were hyponatremia (8.7%), anemia (8.7%), dyspnea 
      (8.7%), thrombocytopenia (6.5%), dehydration (4.3%), and pneumonia (4.3%). The 
      results indicate that ixazomib is not an effective replacement for bortezomib or 
      carfilzomib for patients with MM who have previously relapsed on other 
      bortezomib/carfilzomib-containing regimens.
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Daniely, David
AU  - Daniely D
AD  - Institute for Myeloma & Bone Cancer Research, Los Angeles, CA.
FAU - Forouzan, Eli
AU  - Forouzan E
AD  - Oncotherapeutics, Los Angeles, CA.
FAU - Spektor, Tanya M
AU  - Spektor TM
AD  - Oncotherapeutics, Los Angeles, CA.
FAU - Cohen, Alexa
AU  - Cohen A
AD  - Oncotherapeutics, Los Angeles, CA.
FAU - Bitran, Jacob D
AU  - Bitran JD
AD  - Oncology Specialists SC, Park Ridge, IL.
FAU - Chen, Gigi
AU  - Chen G
AD  - John Muir Medical Center, Walnut Creek, CA.
FAU - Moezi, Mehdi M
AU  - Moezi MM
AD  - Cancer Specialists of North Florida, Fleming Island, FL.
FAU - Bessudo, Alberto
AU  - Bessudo A
AD  - California Cancer Associates for Research & Excellence (cCARE), Encinitas, CA.
FAU - Hrom, John
AU  - Hrom J
AD  - Hattiesburg Clinic of Hematology and Oncology, Hattiesburg, MS.
FAU - Eshaghian, Shahrooz
AU  - Eshaghian S
AD  - Compassionate Oncology Medical Group, Los Angeles, CA.
FAU - Swift, Regina A
AU  - Swift RA
AD  - James R. Berenson, MD, Inc., Los Angeles, CA.
FAU - Eades, Benjamin M
AU  - Eades BM
AD  - James R. Berenson, MD, Inc., Los Angeles, CA.
FAU - Kim, Clara
AU  - Kim C
AD  - Oncotherapeutics, Los Angeles, CA.
FAU - Lim, Stephen
AU  - Lim S
AD  - Cedars-Sinai Cancer Center, West Hollywood, CA.
FAU - Berenson, James R
AU  - Berenson JR
AD  - Institute for Myeloma & Bone Cancer Research, Los Angeles, CA; Oncotherapeutics, 
      Los Angeles, CA; James R. Berenson, MD, Inc., Los Angeles, CA. Electronic 
      address: jberenson@berensoncancercenter.com.
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 - 20220410
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Boron Compounds)
RN  - 0 (Oligopeptides)
RN  - 69G8BD63PP (Bortezomib)
RN  - 71050168A2 (ixazomib)
RN  - 72X6E3J5AR (carfilzomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Boron Compounds
MH  - Bortezomib
MH  - Dexamethasone/adverse effects
MH  - Glycine/analogs & derivatives
MH  - Humans
MH  - *Multiple Myeloma/drug therapy
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Oligopeptides
COIS- Conflict of interest disclosure This study was funded by Takeda Pharmaceutical 
      Company Limited and performed by the clinical research organization 
      Oncotherapeutics.
EDAT- 2022/04/14 06:00
MHDA- 2022/06/22 06:00
CRDT- 2022/04/13 20:06
PHST- 2022/02/25 00:00 [received]
PHST- 2022/04/04 00:00 [revised]
PHST- 2022/04/05 00:00 [accepted]
PHST- 2022/04/14 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/04/13 20:06 [entrez]
AID - S0301-472X(22)00157-6 [pii]
AID - 10.1016/j.exphem.2022.04.003 [doi]
PST - ppublish
SO  - Exp Hematol. 2022 Jul;111:79-86. doi: 10.1016/j.exphem.2022.04.003. Epub 2022 Apr 
      10.