title: Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients.
abstract: The ubiquitin-proteasome pathway regulates bone formation through osteoblast differentiation. We analyzed variation alkaline phosphatase (ALP) during carfilzomib treatment. Data from 38 patients enrolled in the PX-171-003 and 29 patients in PX-171-004 studies, for patients with relapsed/refractory myeloma, were analyzed. All patients received 20 mg/m(2) of carfilzomib on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Sixty-seven patients from ALP data were evaluable. In PX-171-003, the ORR (>PR) was 18% and the clinical benefit response (CBR; >MR) was 26%, while in PX-171-004, the ORR was 35.5% overall and 57% in bortezomib-naive patients. ALP increment from baseline was statistically different in patients who achieved ≥ VGPR compared with all others on Days 1 (P = 0.0049) and 8 (P = 0.006) of Cycle 2. In patients achieving a VGPR or better, ALP increased more than 15 units per liter at Cycle 2 Day 1 over baseline. An ALP increase over the same period of time was seen in 26%, 13% and 11% of patients achieving PR, MR, and SD, respectively. This retrospective analysis of patients with relapsed or refractory myeloma treated with single-agent carfilzomib indicates that early elevation in ALP is associated with subsequent myeloma response.
authors.affiliation: Division of Hematology, University of Utah, Blood/Marrow Transplant and Myeloma Program, Salt Lake City, UT, USA. maurizio.zangari@hsc.utah.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Monette
authors.initials: M
authors.lastname: Aujay
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Hetherington
authors.forename: Tamara
authors.initials: T
authors.lastname: Berno
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.forename: A
authors.initials: A
authors.lastname: Keith Stewart
authors.forename: Luhua
authors.initials: L
authors.lastname: Wang
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Andrew
authors.initials: A
authors.lastname: Belch
authors.forename: Andrzej
authors.initials: A
authors.lastname: Jakubowiak
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.forename: Suzanne
authors.initials: S
authors.lastname: Trudel
authors.forename: Nizar
authors.initials: N
authors.lastname: Bahlis
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology*; D009842:Oligopeptides / Q000627:therapeutic use*; D010012:Osteogenesis / Q000187:drug effects; D011480:Protease Inhibitors / Q000627:therapeutic use; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; C524865:carfilzomib; D000469:Alkaline Phosphatase