Risk of acute myeloid leukemia and myelodysplastic syndromes following multiple myeloma and its precursor disease (MGUS).

Using population-based data from Sweden, we identified all multiple myeloma (MM) patients (n=8,740) and 5652 monoclonal gammopathy of undetermined significance (MGUS) patients diagnosed 1986-2005. We calculated standardized incidence rates (SIRs) for all subsequent hematologic and non-hematologic malignancies, for MM patients diagnosed before/after 1995 (introduction of high-dose melphalan/autologous stem-cell transplant; HDM-ASCT) and 2000 (introduction of immunomodulatory drugs; IMiDs), respectively. MM patients had an 11.51-fold (95% confidence interval: 8.19-15.74) increased risk of acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS); risk was very similar before/after 1995 and 2000, respectively. MGUS patients had an 8.01-fold (5.40-11.43) increased risk of AML/MDS; risk was confined to IgG/IgA, while no IgM MGUS patients developed AML/MDS; patients with monoclonal-(M)-protein concentrations >1.5 g/dL (SIR=11.12;3.61-25.96) had higher risk than those <1.5 g/dL (SIR=4.67;1.71-10.16). An excess risk of non-melanoma skin cancer was observed subsequent to both MM (SIR=2.22;1.74-2.80) and MGUS (SIR=3.30;2.76-3.90). Our novel observations of an excess risk for AML/MDS following IgG/IgA (but not IgM) MGUS, and the highest risk associated with M-protein concentrations >1.5 g/dL, support a role for non-treatment related factors in plasma-cell dyscrasias. AML/MDS risk following MM was the same before/after the introduction of HDM-ASCT. Longer follow-up is needed to characterize second tumor risks in the IMiD-era. [ABSTRACT FROM AUTHOR]