PMID- 33638035
OWN - NLM
STAT- MEDLINE
DCOM- 20210531
LR  - 20210531
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 113
IP  - 6
DP  - 2021 Jun
TI  - A phase I, dose-escalation study of oral PIM447 in Japanese patients with 
      relapsed and/or refractory multiple myeloma.
PG  - 797-806
LID - 10.1007/s12185-021-03096-9 [doi]
AB  - PIM447, a pan-proviral integration site for Moloney leukemia (PIM) kinase 
      inhibitor, has shown preclinical activity in multiple myeloma (MM). This phase I, 
      open-label, multicenter, dose-escalation study aimed to determine the maximum 
      tolerated dose (MTD) and recommended dose for expansion (RDE) of PIM447 in 
      Japanese patients with relapsed and/or refractory (R/R) MM. The study included 13 
      patients (250 mg once daily (QD), [n = 7]; 300 mg QD, [n = 6]). The sole 
      dose-limiting toxicity observed was grade 3 QTc prolongation in one patient from 
      the 300 mg group, and the MTD and RDE was not determined. The most common 
      suspected PIM447-related adverse events (AEs) included thrombocytopenia (76.9%), 
      anemia (53.8%), and leukopenia (53.8%). All patients experienced at least one 
      grade 3 or 4 AE, most frequently thrombocytopenia or leukopenia (61.5% each). The 
      overall response rate was 15.4%, disease control rate 69.2%, clinical benefit 
      rate 23.1%, and two patients had a partial response (one in each dose group). Two 
      patients treated with 250 mg QD had a progression-free survival > 6 months. 
      PIM447 250 mg or 300 mg QD was tolerated in Japanese patients with R/R MM. 
      Further studies are required to evaluate clinical outcomes of PIM447 in 
      combination with other drugs for the treatment of MM.Trial registration: 
      clinicaltrials.gov: (NCT02160951).
FAU - Iida, Shinsuke
AU  - Iida S
AUID- ORCID: 0000-0002-4951-960X
AD  - Department of Hematology and Oncology, Nagoya City University Graduate School of 
      Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, 
      Japan. iida@med.nagoya-cu.ac.jp.
FAU - Sunami, Kazutaka
AU  - Sunami K
AD  - Department of Hematology, National Hospital Organization Okayama Medical Center, 
      Okayama, Japan.
FAU - Minami, Hironobu
AU  - Minami H
AD  - Division of Medical Oncology and Hematology, Kobe University Hospital, Kobe, 
      Hyogo, Japan.
FAU - Hatake, Kiyohiko
AU  - Hatake K
AD  - Department of Hematology and Oncology, Cancer Institute Hospital, Japanese 
      Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
FAU - Sekiguchi, Risa
AU  - Sekiguchi R
AD  - Novartis Pharma K.K., Minato-ku, Tokyo, Japan.
FAU - Natsume, Kazuto
AU  - Natsume K
AD  - Novartis Pharma K.K., Minato-ku, Tokyo, Japan.
FAU - Ishikawa, Norifumi
AU  - Ishikawa N
AD  - Novartis Pharma K.K., Minato-ku, Tokyo, Japan.
FAU - Rinne, Mikael
AU  - Rinne M
AD  - Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
FAU - Taniwaki, Masafumi
AU  - Taniwaki M
AD  - Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural 
      University of Medicine, Kyoto, Japan.
AD  - Center for Molecular Diagnostics and Therapeutics, Kyoto Prefectural University 
      of Medicine, Kyoto, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT02160951
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210227
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/enzymology/mortality
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse effects
MH  - Survival Rate
OTO - NOTNLM
OT  - Clinical trials
OT  - Multiple myeloma
OT  - PIM kinase
OT  - PIM447
OT  - Phase I
EDAT- 2021/02/28 06:00
MHDA- 2021/06/01 06:00
CRDT- 2021/02/27 05:41
PHST- 2020/09/03 00:00 [received]
PHST- 2021/01/29 00:00 [accepted]
PHST- 2021/01/29 00:00 [revised]
PHST- 2021/02/28 06:00 [pubmed]
PHST- 2021/06/01 06:00 [medline]
PHST- 2021/02/27 05:41 [entrez]
AID - 10.1007/s12185-021-03096-9 [pii]
AID - 10.1007/s12185-021-03096-9 [doi]
PST - ppublish
SO  - Int J Hematol. 2021 Jun;113(6):797-806. doi: 10.1007/s12185-021-03096-9. Epub 
      2021 Feb 27.