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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.P. Raaijmakers,
M.A.I. Izquierdo,
H.M. Lokhorst,
C. de Leeuw,
J.A.M. Belien,
A.C. Bloem,
A.W. Dekker,
R.J. Scheper, and
P. Sonneveld
From the Departments of Haematology and Immunology, the University
Hospital Utrecht; the Department of Haematology, University Hospital
Rotterdam Dijkzigt, Rotterdam; and the Department of Pathology,
University Hospital Vrije Universiteit, Amsterdam, the Netherlands.
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.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1029-1036
© 1998 by The American Society of Hematology.
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