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- Title
Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients.
- Authors
Zangari, Maurizio; Aujay, Monette; Fenghuang Zhan; Hetherington, Kristina L.; Berno, Tamara; Vij, Ravi; Jagannath, Sundar; Siegel, David; Stewart, A. Keith; Wang, Luhua; Orlowski, Robert Z.; Belch, Andrew; Jakubowiak, Andrzej; Somlo, George; Trudel, Suzanne; Bahlis, Nizar; Lonial, Sagar; Singhal, Seema; Kukreti, Vishal; Tricot, Guido
- 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 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.
- Subjects
ALKALINE phosphatase; MULTIPLE myeloma treatment; UBIQUITIN; PLASMA cell diseases; RETROSPECTIVE studies; HEMATOLOGY
- Publication
European Journal of Haematology, 2011, Vol 86, Issue 6, p484
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/j.1600-0609.2011.01602.x