Macrofocal Multiple Myeloma in Young Patients: A Distinct Entity with Favorable Prognosis.

Introduction: Most patients with multiple myeloma (MM) present with multiple lytic bone lesions, extensive marrow plasmacytosis and anemia. Furthermore in several of them hypercalcemia and renal impairment are evident at diagnosis. Over the years, we have seen occasional young patients with MM who presented with multiple lytic bone lesions but without intervening infiltration of bone marrow i.e. a pattern consisting of macrofocal MM.

Patients and methods: In order to assess the clinical and laboratory features and the outcome of patients with macrofocal MM we performed a retrospective analysis of symptomatic patients with MM ≤40 years of age at diagnosis who received primary treatment over a 20 year period (from January 1, 1985 to December 31, 2004). The diagnosis of macrofocal MM required the presence of lytic bone lesions and the absence of obvious bone marrow plasmacytosis (BMPC<10%) on bone marrow aspirate and/or biopsy.

Results: Among 51 patients ≤40 years at the time of initial treatment, 10 patients fulfilled the criteria of macrofocal MM. Patients’ median age, gender, myeloma heavy and light chain were similar among patients of the 2 groups. When compared with patients with typical MM, patients with macrofocal pattern were less anemic (p=0.018), none had hypercalcemia (p=0.1), renal impairment (p=0.17), elevated serum LDH (p=0.14), or stage 3 according to the International Staging System (ISS) (p=0.13). Four of the 10 patients with macrofocal MM versus 0 of 41 patients with typical MM (p=<0.01) had a prior diagnosis of solitary bone plasmacytoma. Approximately 80% of patients in both groups received primary treatment based on high-dose dexamethasone regimens (VAD or VAD-like regimens). An objective response was noted in 55% of patients with macrofocal MM and in 50% of patients without this pattern. The median survival of patients with typical MM was 57 months and has not been reached in patients with macrofocal MM (p=0.087). In the latter group of patients, median survival is projected to exceed 8 years. The 10 year survival rate is 20% and 5% in patients with or without macrofocal myeloma respecrively.

Conclusion: Our analysis indicates that macrofocal MM is a distinct entity in young patients with MM. Despite multiple lytic bone lesions, such patients have features of low tumor burden and an improved survival when compared with young patients with typical MM. Future studies including gene profiling may reveal potential biological differences among the two groups of patients.