High Serum Lactate Dehydrogenase (LDH) Is An Important Prognostic Factor in the Era of Novel Agents and Adds to the Prognostic Value of the International Staging System (ISS) in Patients with Multiple Myeloma.

Abstract 1819

Poster Board I-845

Several older studies have shown that high serum LDH is associated with features of advanced disease and with an inferior survival of symptomatic patients with MM who require treatment. It is however unclear whether LDH may add to the prognostic value of ISS and whether it may retain its prognostic significance in patients who have been exposed to novel agent-based therapies either at diagnosis or later in the course of their disease. In order to address these issues we analyzed 996 consecutive symptomatic patients who were included in the data base of the Greek Myeloma Study Group and who received frontline treatment between January 1995 and December 2008. Elevated serum LDH to ≥300 IU/L (normal levels <225 IU/L) was observed in 11% of patients. High LDH was seen more often in patients with impaired performance status (p<0.01), with anemia (p<0.01), with thrombocytopenia (p<0.01), with renal impairment (p<0.01), with high ISS (p<0.01), and with hypercalcemia (p=0.01). The median survival of all patients was 40 months with a clear improvement for patients who started treatment after January 2000 as compared to patients who started treatment before that date (50 months versus 31 months; p<0.01). Multiple clilnical and laboratory variables correlated with the probability of survival in univariate analysis. A multivariate analysis showed that the following variables had an independent prognostic significance: LDH (p<0.001), ISS (p<0.001), performance status (p<0.001), age (p<0.001) and platelet count (p<0.001). The median survival of patients with high versus normal LDH was 15 months versus 44 months (p<0.001). High LDH was observed in 7% of patients with ISS-1, in 10% of ISS-2 and 12% of ISS-3. Within each ISS subgroup the presence of high LDH was associated with a worse median survival. In ISS-1 the median survival of patients with high LDH was 22 months (CI 95%: 10-35) while the median survival of those with normal LDH was 76 months (CI 95%: 61-91; p<0.01). Similarly in ISS-2 the median survival of patients with high and normal LDH was 11 months (CI 95%: 7-14) and 40 months (CI 95%: 32-48), respectively (p<0.001), while in ISS-3 it was 17 months (CI 95%: 11-23) and 27 months (CI 95%: 21-33), respectively (p<0.01). Subsequently, patients were separated into two groups: patients who started treatment between January 1995 and December 1999 and patients who started therapy after January 2000 i.e. patients who had access to novel agent-based therapy. In both groups the presence of high LDH was related with statistically worse survival. In patients who received treatment before January 2000, the median survival in the high LDH group was 10 months (CI 95%: 4-16) versus 36 months in the normal LDH group (CI 95%: 31-42; p<0.001). Similarly, in patients who received treatment after January 2000, the median survival in the high LDH group was 21 months (CI 95%: 12-29) versus 51 months in the normal LDH group (CI 95%: 40-63; p<0.001). We conclude that serum LDH is a readily available and inexpensive variable which has a major impact on the survival of patients with myeloma even when they belong to a low or intermediate ISS subgroup and even when they receive novel agent-based therapy.