PMID- 34645759
OWN - NLM
STAT- MEDLINE
DCOM- 20220503
LR  - 20220716
IS  - 1349-7235 (Electronic)
IS  - 0918-2918 (Print)
IS  - 0918-2918 (Linking)
VI  - 61
IP  - 9
DP  - 2022 May 1
TI  - Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma 
      in Japan: An All-case Post-marketing Surveillance.
PG  - 1337-1343
LID - 10.2169/internalmedicine.7768-21 [doi]
AB  - Objective To evaluate the safety profile of ixazomib combined with lenalidomide 
      and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) in 
      clinical practice in Japan through an all-case post-marketing surveillance. 
      Methods This was a nationwide non-interventional observational study conducted in 
      Japan. The study included all patients who received ixazomib from May 24 to 
      September 24, 2017. Ixazomib was administered to RRMM patients according to the 
      Japanese package insert. All enrolled patients were observed until the completion 
      of the sixth treatment cycle or until ixazomib discontinuation. The patient 
      treatment course, including adverse events (AEs), was reported. Results The 
      safety analysis set included 741 patients; the median age was 71 (range 35-92) 
      years old, and the median number of prior treatment lines was 3 (range 1-30). 
      Adverse drug reactions (ADRs) occurred in 572 (77.2%) patients, most commonly 
      being thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Serious 
      ADRs occurred in 193 (26.0%) patients, most commonly being thrombocytopenia 
      (9.9%) and diarrhea (5.9%). Thrombocytopenia, severe gastrointestinal disorders, 
      infections, skin disorders, and peripheral neuropathy were prespecified as ADRs 
      of clinical importance; the frequency of these ADRs (grade >/=3) were 28.5%, 9.4%, 
      7.4%, 2.2%, and 1.3%, respectively. Treatment discontinuation was most common 
      with thrombocytopenia and severe gastrointestinal disorders (49 and 43 patients, 
      respectively). Eleven patients died due to ADRs (16 events). Conclusion These 
      results suggest that ixazomib has a tolerable safety profile in clinical practice 
      in Japan. However, close AE management for thrombocytopenia and gastrointestinal 
      disorders should be considered.
FAU - Kakimoto, Yoshihide
AU  - Kakimoto Y
AD  - Japan Medical Affairs, Japan Oncology Business Unit, Takeda Pharmaceutical 
      Company Limited, Japan.
FAU - Hoshino, Miyako
AU  - Hoshino M
AD  - Japan Medical Office, Japan Pharma Business Unit, Takeda Pharmaceutical Company 
      Limited, Japan.
FAU - Hashimoto, Mikiko
AU  - Hashimoto M
AD  - Japan Medical Office, Japan Pharma Business Unit, Takeda Pharmaceutical Company 
      Limited, Japan.
FAU - Hiraizumi, Masaya
AU  - Hiraizumi M
AD  - Pharmacovigilance, Takeda Development Center Japan, Takeda Pharmaceutical Company 
      Limited, Japan.
FAU - Shimizu, Kohei
AU  - Shimizu K
AD  - Biostatistics, Takeda Development Center Japan, Takeda Pharmaceutical Company 
      Limited, Japan.
FAU - Chou, Takaaki
AU  - Chou T
AD  - Department of Internal Medicine, Niigata Cancer Center Hospital, Japan.
AD  - Niigata Kenshin Plaza, General Incorporated Foundation, Health Medicine 
      Prevention Association, Japan.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20211012
PL  - Japan
TA  - Intern Med
JT  - Internal medicine (Tokyo, Japan)
JID - 9204241
RN  - 0 (Boron Compounds)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 71050168A2 (ixazomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Boron Compounds
MH  - Dexamethasone/therapeutic use
MH  - Diarrhea/chemically induced/epidemiology
MH  - Glycine/analogs & derivatives
MH  - Humans
MH  - Japan
MH  - *Leukopenia/chemically induced
MH  - Middle Aged
MH  - *Multiple Myeloma/drug therapy/etiology
MH  - Product Surveillance, Postmarketing
MH  - Thalidomide/therapeutic use
MH  - *Thrombocytopenia/chemically induced/drug therapy/epidemiology
PMC - PMC9152867
OTO - NOTNLM
OT  - adverse drug reaction
OT  - ixazomib
OT  - multiple myeloma
OT  - post-marketing all-case surveillance
OT  - proteasome inhibitor
OT  - safety
COIS- Author's disclosure of potential Conflicts of Interest (COI). Yoshihide Kakimoto: 
      Employment, Takeda Pharmaceutical. Miyako Hoshino: Employment, Takeda 
      Pharmaceutical. Mikiko Hashimoto: Employment, Takeda Pharmaceutical. Masaya 
      Hiraizumi: Employment, Takeda Pharmaceutical. Kohei Shimizu: Employment, Takeda 
      Pharmaceutical. Takaaki Chou: Honoraria, Takeda Pharmaceutical, Janssen 
      Pharmaceuticals, Celgene and BMS.
EDAT- 2021/10/15 06:00
MHDA- 2022/05/04 06:00
PMCR- 2022/05/01
CRDT- 2021/10/14 05:46
PHST- 2021/10/15 06:00 [pubmed]
PHST- 2022/05/04 06:00 [medline]
PHST- 2021/10/14 05:46 [entrez]
PHST- 2022/05/01 00:00 [pmc-release]
AID - 10.2169/internalmedicine.7768-21 [doi]
PST - ppublish
SO  - Intern Med. 2022 May 1;61(9):1337-1343. doi: 10.2169/internalmedicine.7768-21. 
      Epub 2021 Oct 12.