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.
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.
Raaijmakers
H G
HG
Departments of Haematology and Immunology, University Hospital Utrecht, The Netherlands.
Izquierdo
M A
MA
Lokhorst
H M
HM
de Leeuw
C
C
Belien
J A
JA
Bloem
A C
AC
Dekker
A W
AW
Scheper
R J
RJ
Sonneveld
P
P
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
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan; D009363:Neoplasm Proteins; D011241:Prednisone; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein