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Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients
Author(s) -
Zangari Maurizio,
Aujay Monette,
Zhan Fenghuang,
Hetherington Kristina L.,
Berno Tamara,
Vij Ravi,
Jagannath Sundar,
Siegel David,
Keith Stewart A.,
Wang Luhua,
Orlowski Robert Z.,
Belch Andrew,
Jakubowiak Andrzej,
Somlo George,
Trudel Suzanne,
Bahlis Nizar,
Lonial Sagar,
Singhal Seema,
Kukreti Vishal,
Tricot Guido
Publication year - 2011
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2011.01602.x
Subject(s) - carfilzomib , multiple myeloma , oncology , variation (astronomy) , alkaline phosphatase , medicine , chemistry , lenalidomide , biochemistry , enzyme , physics , astrophysics
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.