title: Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients.
abstract: Myeloma bone disease is characterized by osteolytic destruction associated with suppressed osteoblastic activity. Using data from the APEX (Richardson et al., N Engl J Med 2005;352:2487-2498) study, we have assessed the relationship of changes in alkaline phosphatase (ALP) levels during bortezomib therapy with response and time to progression on this therapy. The percentage of ALP increments in responders (complete and partial response) and nonresponders was analyzed at different thresholds and time points. For all bortezomib-treated patients enrolled in the trial (N = 333), at least a 25% increase in ALP from the baseline at 6 week was the most powerful predictor of treatment response (P < 0.0001) and time to progression (206 vs. 169 days) relative to patients with less than a 25% increase in ALP (P = 0.01). Markers of osteoblastic activation may predict quality and duration of response in multiple myeloma. In addition, our data suggest that bone anabolism could inhibit myeloma growth.
authors.affiliation: The Myeloma Institute for Research and Therapy, The University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. zangarimaurizio@uams.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Dixie
authors.initials: D
authors.lastname: Esseltine
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Rachel
authors.initials: R
authors.lastname: Neuwirth
authors.forename: Francesca
authors.initials: F
authors.lastname: Elice
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Burns
authors.forename: Shmuel
authors.initials: S
authors.lastname: Yaccoby
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis* / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D001897:Boronic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D000069286:Bortezomib; D016009:Chi-Square Distribution; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy*; D010006:Osteoblasts / Q000378:metabolism; D011237:Predictive Value of Tests; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D001897:Boronic Acids; D011719:Pyrazines; D001613:beta 2-Microglobulin; D000069286:Bortezomib; D003907:Dexamethasone; D000469:Alkaline Phosphatase