Prognostic Factors and Outcome of Older Patients with Symptomatic Multiple Myeloma: A Study of the Greek Myeloma Study Group (GMSG).

Introduction: Prospective randomized trials have shown that high dose therapy with autologous stem cell transplantation may improve the survival of patients with multiple myeloma (MM). This procedure is usually applied to patients ≤70 years of age. Nevertheless, many patients with MM are diagnosed at an older age and are usually treated with conventional chemotherapy. We performed a retrospective analysis in order to compare the prognostic factors and outcome of younger patients with myeloma (≤ 70 years) with those of older patients (>70 years). We also applied the recently proposed International Staging System (ISS) for multiple myeloma in the two groups of patients.

Patients and Methods: Since 1987, 1162 patients with symptomatic myeloma requiring treatment have been included in the data base of GMSG. Patients with asymptomatic myeloma were not included. 357 patients (31%) were > 70 years at the time of initial treatment. Multiple clinical and laboratory variables were evaluated in patients >70 years of age and in younger patients. Furthermore, the same variables were assessed for possible correlation with prognosis in patients >70 years of age.

Results: The only variable that was different between the two groups of patients was the ISS with older patients presenting more often with advanced ISS (p=0.02). Older patients received more often primary treatment with standard alkylating agents - corticosteroid combinations whereas younger patients received more often primary treatment based on high dose pulse dexamethasone (VAD etc) (p=0.001). Response to treatment was similar but patients ≤ 70 years had a median survival of 40 months versus 29 months for older patients (p<0.001). Variables associated with shorter survival for the group of older patients were: anemia, thrombocytopenia, hypercalcemia, renal impairment, more extensive bone marrow plasmacytosis, elevated serum LDH and advanced ISS (2+3). A Cox regression analysis showed, that adjusting for the effects of other factors, elevated LDH, bone marrow plasmacytosis and advanced ISS retained prognostic significance in this group of older patients (median survival of 12 months, 22 months and 21 months respectively). However patients >70 years of age with ISS 1 had a relatively long median survival of 55 months.

Conclusions: The clinical and laboratory characteristics of older patients with MM are similar to those of younger patients but older patients tend to present with more advanced ISS. The survival of older patients is shorter than that of younger patients. Elevated serum LDH, advanced ISS, and increased bone marrow plasmacytosis may identify older patients with particularly bad prognosis. Older patients with poor prognosis should be entered into clinical trials in order to see if treatment with new agents or combinations would prolong their survival. The application of ISS in patients >70 years of age permitted the identification at diagnosis of a subgroup of patients with ISS 1 who had a relatively good prognosis.