PMID- 33421178
OWN - NLM
STAT- MEDLINE
DCOM- 20210423
LR  - 20210423
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Print)
IS  - 0361-8609 (Linking)
VI  - 96
IP  - 4
DP  - 2021 Apr 1
TI  - A phase I/II study of the combination of panobinostat and carfilzomib in patients 
      with relapsed or relapsed/refractory multiple myeloma: Final analysis of second 
      dose-expansion cohort.
PG  - 428-435
LID - 10.1002/ajh.26088 [doi]
AB  - The maximum tolerated dose of the panobinostat and carfilzomib combination in 
      patients with relapsed/refractory multiple myeloma (RRMM) was not reached in our 
      previous dose-escalation study. We report additional dose levels in the phase 
      I/II, single-arm, multicenter, standard 3 + 3 dose-escalation expansion-cohort 
      study (NCT01496118). Patients with RRMM were treated with panobinostat 30 mg, 
      carfilzomib 20/56 mg/m(2) (N = 3), or panobinostat 20 mg, carfilzomib 
      20/56 mg/m(2) (N = 33). Treatment cycles lasted 28 days; panobinostat: days 1, 3, 
      5, 15, 17, 19; carfilzomib: days 1, 2, 8, 9, 15, 16. For dose level 6 (DL 6), 
      median age was 63 years (range, 49-91 years), 60.6% were male, 42.4% were high 
      risk. Patients received a median of two prior therapies (range 1-7); proteasome 
      inhibitors (PI; 100%), immunomodulatory imide drugs (IMiD; 78.8%), and stem cell 
      transplant (36.4%); 48.5%, 51.1%, and 24.2% were refractory to prior PI or prior 
      IMiD treatment or both, respectively. Patients completed a median of seven (range 
      1-40) treatment cycles. Overall response rate (primary endpoint) of evaluable 
      patients in the expansion cohort (N = 32): 84.4%; clinical benefit rate: 90.6%. 
      With a median follow-up of 26.1 months (range, 0-72.5 months), median (95% CI) 
      progression-free survival, time-to-progression and overall survival of patients 
      was 10.3 (6.1, 13.9), 11.7 (5.6, 14.5), and 44.6 (20.8, N/A) months, 
      respectively. Common adverse events (AEs) included thrombocytopenia (78.8%), 
      nausea (63.6%), fatigue (63.6%), diarrhea (51.5%), and vomiting (51.5%). Seven 
      patients had serious treatment-related AEs. There was one treatment-related 
      death. In conclusion, panobinostat plus carfilzomib is an effective 
      steroid-sparing regimen for RRMM.
CI  - (c) 2021 The Authors. American Journal of Hematology published by Wiley Periodicals 
      LLC.
FAU - Berdeja, Jesus G
AU  - Berdeja JG
AUID- ORCID: 0000-0003-4362-0376
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Tennessee Oncology PLLC, Nashville, Tennessee.
FAU - Gregory, Tara K
AU  - Gregory TK
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Colorado Blood Cancer Institute, Denver, Colorado.
FAU - Faber, Edward A
AU  - Faber EA
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Oncology Hematology Care, Cincinnati, Ohio.
FAU - Hart, Lowell L
AU  - Hart LL
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Florida Cancer Specialists, Fort Myers, Florida.
FAU - Mace, Joseph R
AU  - Mace JR
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Florida Cancer Specialists, St. Petersburg, Florida.
FAU - Arrowsmith, Edward R
AU  - Arrowsmith ER
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Tennessee Oncology PLLC, Chattanooga, Tennessee.
FAU - Flinn, Ian W
AU  - Flinn IW
AUID- ORCID: 0000-0001-6724-290X
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Tennessee Oncology PLLC, Nashville, Tennessee.
FAU - Matous, Jeffrey V
AU  - Matous JV
AD  - Sarah Cannon Research Institute, Nashville, Tennessee.
AD  - Colorado Blood Cancer Institute, Denver, Colorado.
LA  - eng
SI  - ClinicalTrials.gov/NCT01496118
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 - 20210128
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (Oligopeptides)
RN  - 72X6E3J5AR (carfilzomib)
RN  - 9647FM7Y3Z (Panobinostat)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Gastrointestinal Diseases/chemically induced
MH  - Hematologic Diseases/chemically induced
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
MH  - Oligopeptides/administration & dosage/adverse effects
MH  - Panobinostat/administration & dosage/adverse effects
MH  - Premedication
MH  - Progression-Free Survival
MH  - *Salvage Therapy
PMC - PMC7986798
EDAT- 2021/01/10 06:00
MHDA- 2021/04/24 06:00
PMCR- 2021/03/23
CRDT- 2021/01/09 17:09
PHST- 2020/09/15 00:00 [received]
PHST- 2020/12/16 00:00 [revised]
PHST- 2021/01/02 00:00 [accepted]
PHST- 2021/01/10 06:00 [pubmed]
PHST- 2021/04/24 06:00 [medline]
PHST- 2021/01/09 17:09 [entrez]
PHST- 2021/03/23 00:00 [pmc-release]
AID - AJH26088 [pii]
AID - 10.1002/ajh.26088 [doi]
PST - ppublish
SO  - Am J Hematol. 2021 Apr 1;96(4):428-435. doi: 10.1002/ajh.26088. Epub 2021 Jan 28.