Prognostic values of lung resistance protein (LRP) and P53 in patients with multiple myeloma (MM)

Abstract

8113 Background: This study was undertaken to assess the significance of lung-resistance related protein (LRP) expression and p53 mutations in plasma cells from untreated multiple myeloma (MM) patients and to determine whether LRP expression and p53 deletions was associated with a poor response and survival in patients treated with a conventional dose of melphalan. Methods: We have studied LRP expression by immunocytochemistry and p53 deletions by interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 in bone marrow plasma cells from 38 untreated patients with MM received conventional oral dose melphalan (0.25 mg/kg, day 1 to 4) combined with prednisone (MP). We also studied their association with both response to chemotherapy and survival of the patients. Results: By FISH, deletions of p53, were detected in 31.5% of patients and LRP was found positive in 36.8%. Patients with a p53 deletion were predominantly at stage III (p53 deletion in 83.4% of stage III patients vs. 8.3% of patients at stages I and II respectively; P = 0.04). Both p53 deletion and LRP expression were correlated with other laboratory and clinical parameters. The overall response rate of all of the evaluable patients was 63.2%. The response rate was 79.2% for patients without LRP expression but only 35.7% for patients with LRP expression (P = 0.01). Among the 12 patients with a p53 deletion by FISH, 25% responded compared with 75% of patients without p53 deletion (P = 0.001). With the exception of LRP expression and p53 deletions, there was no other prognostic variable sharing any correlation with response. The median survival of LRP-positive patients was 11 months (95%-Cl: 9 to 24), whereas the median survival duration of LRP negative patients was not reached (Cl: 26 to 82; P < .002; hazard ratio [HR] = 2.9 (1.4–5.7). Patients with and without p53 deletions had significantly different overall survival times (median 13.9 months, 95%-CI: 8 to 26 and median not reached, CI: 24 to84, respectively; P < .0001; hazard ratio [HR] = 2.6). Conclusions: For patients with MM who were treated with conventional-dose chemotherapy, LRP expression and p53 deletions provides prognostically relevant information in addition to that provided by standard prognostic factors. No significant financial relationships to disclose.