Validation of the International Prognostic Scoring System (IPSS) for Waldenstrom's Macroglobulinemia (WM) and the Importance of Serum Lactate Dehydrogenase (LDH).

Abstract 2845

Poster Board II-821

Recently, the IPSS has been proposed as a staging system for patients with WM who require treatment. This system is based on five adverse covariates: age >65 years, hemoglobin '11.5 g/dL, platelet count '100×10⁹/L, beta2-microglobulin >3 mg/L and serum monoclonal protein concentration >7 g/dL. Low risk is defined by the presence of ' 1 adverse characteristic and age '65 years, intermediate risk by the presence of 2 adverse characteristics or only age >65 years and high risk by the presence of >2 adverse characteristics. The aim of our analysis was to independently validate the significance of IPSS not only for overall survival (OS) but also for cause-specific survival (CSS) (i.e deaths unrelated to WM or to complications of treatment are censored). Furthermore, we wanted to assess whether elevated serum LDH may add to the strength of IPSS. From the data base of the Greek Myeloma Study Group, we identified 335 patients with clearly defined criteria for diagnosis and for initiation of treatment who were treated over the last 20 years. Main primary therapies included alkylating agents (43%), CHOP (3%), nucleoside analogues (3%) and rituximab either alone (3%) or in combination with conventional chemotherapy (44%). Before the initiation of treatment the median age of patients was 68 years (range 28 to 89 years). Fifty-nine percent of patients were >65 years, while 75% of patients had hemoglobin levels of <11.5 g/dL, 57% had beta2-microglobulin of >3 mg/L, 33% had lymphadenopathy, 32% splenomegaly, 23% presence of B-symptoms, 12% platelet count of <100×10⁹/L and 6% had serum monoclonal protein concentration of >7 g/dL. Among 152 patients who had died by the time of this analysis, 33 patients (22%) had died due to causes not related to WM, to disease transformation, to myelodysplasia or to complications of treatment. Most frequent causes were second primary solid tumors, celebrovascular accidents, coronary artery disease and congestive heart failure. For the whole group of patients median OS was 105 months and median CSS was 116 months. Patients were divided into low risk (23%), intermediate risk (38%) and high risk (39%), according to IPSS. Median OS was 161 months, 105 months and 64 months respectively (p<0.01) and median CSS was 172 months, 116 months and 94 months, respectively (p<0.01). Elevated serum LDH >250 IU/L (normal upper limit 225 IU/L) was found in 18% of patients. Serum LDH was elevated in 16%, 12% and 24% of patients with low, intermediate and high risk, respectively. Median OS according to low or elevated LDH was 109 versus 63 months (p<0.01) and median CSS was 116 versus 64 months, respectively (p<0.01). Serum LDH was able to divide high risk patients into two subgroups with different outcome. The median OS was 94 and 35 months, for normal and high LDH group, respectively (p<0.01) and the median CSS was 104 and 36 months, for normal and high LDH group, respectively (p<0.01). We conclude that the recently proposed IPSS for WM is a robust staging system and it is also applicable to patients who received primary treatment with rituximab-based regimens. Elevated serum LDH is an adverse prognostic factor in WM. The combination of high risk according to IPSS and elevated serum LDH identified a subset of patients with very poor outcome. Such patients should be included in trials that evaluate novel agents and new treatment strategies including upfront high dose therapy.