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

H G Raaijmakers, M A Izquierdo, H M Lokhorst, C de Leeuw, J A Belien, A C Bloem, A W Dekker, R J Scheper, P Sonneveld

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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.

Original languageEnglish
Pages (from-to)1029-36
Number of pages8
Issue number3
Publication statusPublished - 1 Feb 1998


  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Combined Chemotherapy Protocols
  • Bone Marrow Cells
  • Disease-Free Survival
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Journal Article
  • Male
  • Melphalan
  • Middle Aged
  • Multiple Myeloma
  • Neoplasm Proteins
  • Plasma Cells
  • Prednisone
  • Prognosis
  • Remission Induction
  • Survival Rate
  • Treatment Outcome
  • Vault Ribonucleoprotein Particles

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