Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients

Maurizio Zangari, Monette Aujay, Fenghuang Zhan, Kristina L. Hetherington, Tamara Berno, Ravi Vij, Sundar Jagannath, David Siegel, A. Keith Stewart, Luhua Wang, Robert Z. Orlowski, Andrew Belch, Andrzej Jakubowiak, George Somlo, Suzanne Trudel, Nizar Bahlis, Sagar Lonial, Seema Singhal, Vishal Kukreti, Guido Tricot

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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 20mg/m2 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.

Original languageEnglish
Pages (from-to)484-487
Number of pages4
JournalEuropean Journal of Haematology
Issue number6
StatePublished - Jun 2011


  • Alkaline phosphatase
  • Carfilzomib
  • Multiple myeloma


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