title: Lung-resistance-related protein expression is a negative predictive factor for response to conventional low but not to intensified dose alkylating chemotherapy in multiple myeloma.
abstract: This study was undertaken to assess the significance of lung-resistance related protein (LRP) expression in plasma cells from untreated multiple myeloma (MM) patients and to determine whether LRP was associated with a poor response and survival in patients treated with different dose regimens of melphalan. Seventy untreated patients received conventional oral dose melphalan (0.25 mg/kg, day 1 to 4) combined with prednisone (MP) or intravenous intermediate-IDM; 70 mg/m2) or high- (140 mg/m2) dose Melphalan (HDM). LRP expression was assessed with immunocytochemistry using the LRP-56 monoclonal antibody. LRP expression was found in 47% of patients. In the MP treated patients, LRP expression was a significant prognostic factor regarding response induction (P < .05), event free survival (P < .003), and overall survival (P < .001). In the intensified dose melphalan treated patients LRP did not have a prognostic value. The response rates of LRP-positive patients to MP and IDM/HDM were 18% versus 81%, respectively (P < .0001). We conclude that LRP is frequently expressed in untreated MM patients and is an independent predictor for response and survival in patients treated with MP. Pretreatment assessment of LRP identifies a subpopulation of patients with a poor probability of response to conventional dose melphalan. Dose intensification of melphalan is likely to overcome LRP-mediated resistance.
authors.affiliation: Departments of Haematology and Immunology, University Hospital Utrecht, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Raaijmakers
authors.forename: M A
authors.initials: MA
authors.lastname: Izquierdo
authors.forename: H M
authors.initials: HM
authors.lastname: Lokhorst
authors.forename: C
authors.initials: C
authors.lastname: de Leeuw
authors.forename: J A
authors.initials: JA
authors.lastname: Belien
authors.forename: A C
authors.initials: AC
authors.lastname: Bloem
authors.forename: A W
authors.initials: AW
authors.lastname: Dekker
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000737:chemistry; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis*; D010950:Plasma Cells / Q000737:chemistry; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan; D009363:Neoplasm Proteins; D011241:Prednisone; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein