Multiple Myeloma (MM) is a malignant lymphoproliferative B-cell disease characterized by the accumulation of monoclonal plasma cells in the bone marrow. Acquired genomic aberrations have been shown to significantly impact response to chemotherapy and survival in MM. The aim of our study was to assess the clinical relevance of genomic abnormalities in 306 MM patients treated with high-dose chemotherapy (HDCT) and peripheral stem cell transplantation (PBSCT) in our center.

We analyzed 171 males and 135 females with a median age of 60 years (range 25 – 73 years). According to the international staging system (ISS), MM patients were classified as stage I (46.6%), stage II (36.1%) and stage III (17.4%) at the onset of chemotherapy. All patients underwent frontline HDCT with 200 melphalan mg/m2 and PBSCT according or in analogy to the GMMG-HD3- or GMMG-HD4-trials. Interphase-FISH-analysis was performed on CD138-purified plasma cells using probes for chromosomes 1q21, 6q21, 8p21, 9q34, 11q23, 13q14.3, 15q22, 17p13, 19q13, and 22q11, as well as IgH-translocations t(4;14)(p16.3;q32.3) and t(11;14)(q13;q32.3). For the entire group, the median overall survival (OS) and progression-free survival (PFS) after HDCT was 6.4 and 2.2 years, respectively.

Table 1. Chromosomal abnormalities with significant results (a-level=0.05) on PFS or OS (univariate analysis, unadjusted p-values)

Aberration yesvs.noFrequency %3-year PFS %P value3-year OS %P value
del(8p21) 19 26 vs. 37 0.01 58 vs. 78 0.02 
del(13q14.3) 46 23 vs. 53 <0.001 65 vs. 83 0.03 
del(17p13) 10 22 vs. 40 0.02 44 vs. 82 <0.001 
t(4;14) 14 10 vs. 42 <0.001 54 vs. 81 0.04 
+1q21 35 20 vs. 46 <0.001 67 vs. 85 0.002 
+19q13 54 49 vs. 22 0.03 76 vs. 73 0.92 
Aberration yesvs.noFrequency %3-year PFS %P value3-year OS %P value
del(8p21) 19 26 vs. 37 0.01 58 vs. 78 0.02 
del(13q14.3) 46 23 vs. 53 <0.001 65 vs. 83 0.03 
del(17p13) 10 22 vs. 40 0.02 44 vs. 82 <0.001 
t(4;14) 14 10 vs. 42 <0.001 54 vs. 81 0.04 
+1q21 35 20 vs. 46 <0.001 67 vs. 85 0.002 
+19q13 54 49 vs. 22 0.03 76 vs. 73 0.92 
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In a first step, we analyzed the prognostic impact of each individual chromosomal aberration on PFS and OS (Table 1). After adjustment for the ISS-score, del(8p21), del(13q14.3), del(17p13), t(4;14) as well as gains of 1q21 and 19q13 preserved significant impact on PFS, while del(17p13), t(4;14) and gain of 1q21 were of statistical significance for OS, indicating that these chromosomal aberrations give prognostic information in addition to the ISS-score. Subsequently, we performed a multivariate analysis including all the chromosomal aberrations analyzed. While del(17p13) and gain of 1q21 showed significant results on OS, del(13q14.3), del(22q11) and gain of 15q22 were significant for PFS.

In conclusion, our results show that the heterogeneity seen in the clinical course of MM patients after HDCT can be correlated with distinct chromosomal aberrations. This analysis may have implications for the risk-adopted management of patients with MM.

Topics:
chromosome abnormality, injury severity score, multiple myeloma, peripheral blood stem cell transplantation, chemotherapy regimen, idiopathic guttate hypomelanosis, immunoglobulin heavy chains, melphalan, translocation (genetics), plasma cells

Disclosures: No relevant conflicts of interest to declare.

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2008, The American Society of Hematology
2008
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