Prognostic features of asymptomatic multiple myeloma D ONNA M. WEBER ,MELETIOS A. D IMOPOULOS ,L IA A. MOULOPOULOS ,K AY B. D ELASALLE ,T ERRY S MITH AND R AYMOND A LEXANIAN The University of Texas M. D. Anderson Cancer Center, Houston, Texas, U.S.A. Received 28 October 1996; accepted for publication 7 March 1997 Summary. Approximately 20% of patients with multiple myeloma are recognized by chance without significant symptoms. In order to prevent morbidity with timely therapy, reliable criteria are needed that distinguish those likely to show early or late disease progression. Multiple clinical features were assessed in 101 consecutive, asympto- matic and previously untreated patients. Patients with one or more lytic bone lesions were excluded because this feature had been found previously to be associated with early progression. Multivariate analysis indicated that only serum myeloma globulin >30 g/l, IgA protein type, and Bence Jones protein excretion >50 mg/d remained as significant inde- pendent variables. The presence of two or more of these features signified high-risk disease with early progression (median 17 months) whereas the absence of any adverse variable was associated with prolonged stability (median 95 months) ðP < 0·01Þ. Magnetic resonance (MR) imaging of the spine was useful only in patients with one adverse feature and an intermediate time to progression (median 39 months). An abnormal pattern (40% of patients) helped to distinguish patients with an imminent complication from those with more stable disease. Because a serious complica- tion (fracture, hypercalcaemia) occurred in 35% of patients with early disease progression, chemotherapy seems justified for selected patients with asymptomatic disease at diagnosis. The remaining patients were at such low risk for progression (median 6 years) that they may be followed safely at long intervals without treatment. Keywords: asymptomatic, multiple myeloma, prognosis, magnetic resonance imaging, survival. Most patients with multiple myeloma require chemotherapy at diagnosis because of symptoms due to a pathologic fracture, anaemia, renal impairment or hypercalcaemia. With more frequent screening of apparently normal subjects, more patients have been diagnosed by chance in recent years and a high percentage have been followed safely for long periods without treatment. Various terms, including smouldering myeloma, indolent myeloma and asymptomatic myeloma, have been used to denote disease with marrow plasmacytosis >10% and serum M protein > 25 g/l, which cannot be classified as MGUS, but which may remain stable for long periods without treatment. Multiple myeloma that remained stable for >5 years has been described as smouldering (Kyle & Greipp, 1980); we have described similar patients whose disease was asymptomatic at diagnosis but with variable times to disease progression (Alexanian, 1980; Dimopoulos et al, 1993). The term asymptomatic myeloma seems preferable since the definition is restricted to the clinical status at diagnosis and the subsequent clinical course is variable. Various criteria have been proposed to distinguish more precisely between those asymptomatic patients who are likely to remain stable without therapy for a long period and those at high risk for a serious complication, who might benefit from early chemotherapy. These features have included the presence of a lytic bone lesion, a high level of serum myeloma protein, the presence of Bence Jones protein, and an abnormal bone marrow pattern on magnetic resonance (MR) imaging (Wisloff et al, 1991; Dimopoulos et al, 1993; Hjorth et al, 1993; Facon et al, 1995); some have claimed that the haemoglobin level and the degree of bone marrow plasmacytosis were also useful (Facon et al, 1995). Because of conflicting conclusions in regard to the most important features and in order to justify the value of an expensive procedure, such as an MR imaging study, we updated our experience and defined more clearly those patients who required early therapy from those in whom treatment could be delayed safely for many years. MATERIALS AND METHODS Between October 1974 and October 1995 we evaluated 695 consecutive, previously untreated, patients with multiple myeloma and a monoclonal protein on serum British Journal of Haematology , 1997, 97, 810–814 810  1997 Blackwell Science Ltd Correspondence: Dr Raymond Alexanian, University of Texas M. D. Anderson Cancer Center, Box 1, 1515 Holcombe Blvd, Houston, TX 77030, U.S.A.