Elevated Serum Lactate Dehydrogenase (LDH) Should Be Included Among the Variables Which Define High Risk Multiple myeloma
Authors: Dimopoulos Meletios A. , Kastritis Efstathios , Roussou Maria , Gkotzamanidou Maria , Migkou Magdalini , Gavriatopoulou Maria , Gika Dimitra , Matsouka Charis , Mparmparoussi Despoina , Parcharidou Agapi , Terpos Evangelos 
Published: October 2019

Abstract
Abstract 2969
LDH is elevated in approximately 10% of patients with newly-diagnosed, symptomatic, multiple myeloma (MM). In patients treated with conventional chemotherapy, elevated LDH is associated with poor outcome (Dimopoulos et al, Ann Intern Med 1991). In selected patients treated with combinations of novel agents and tandem transplantation, LDH is an independent prognostic factor and is associated with short event free and overall survival even when cytogenetic abnormalities and gene expression signature are considered (Barlogie et al, J Clin Oncol 2010). An analysis from our group has also suggested that LDH improves the prognostic value of the International Scoring System (ISS) for MM (Terpos et al, Eur J Hematol 2010). However, there is limited data about the prognostic importance of elevated LDH in unselected MM patients who have been treated upfront with novel agent-based regimens. To address this issue, we analyzed 180 consecutive, unselected patients from a single center in Athens, Greece, who were treated upfront with novel agent (thalidomide, bortezomib or lenalidomide)-based therapies. Many of these patients had been included in clinical trials; however, several patients who were ineligible because of poor performance status, significant renal impairment or comorbidities were also treated with novel agent-based regimens. Thus, these patients are more representative of the general myeloma population. Fifty-one per cent of our patients were older than 70 years of age. LDH was elevated (≥300 IU/L, upper limit of normal 225 IU/L) in 8% patients before initiation of treatment. Elevated LDH was associated with features of advanced disease such as ISS-3 stage (p=0.063) and impaired renal function (p=0.034). The objective response rate in patients with elevated LDH was 47% and in patients without elevated LDH was 79% (p=0.011). The median overall survival for all patients was 54 months. Elevated LDH was associated with poor outcome (median survival 21 months vs. 56 months for patients with LDH <300 IU/L, p=0.007). Other factors which were associated with inferior survival, in the univariate analysis were age >70 years (p<0.001), Hb <10 g/dl (p<0.001), platelet counts <130,000/ml (p<0.001), corrected serum calcium >11.5 g/dl (p=0.012), ISS-3 stage (p<0.001) and renal impairment (p=0.001). In the multivariate analysis, elevated serum LDH was an independent factor and had a major prognostic impact associated with a 5.4-fold increased risk for death (p<0.001). Furthermore, elevated serum LDH was more often associated with early death. We conclude that in unselected MM patients treated upfront with novel agents, serum LDH is a simple, inexpensive and readily available blood test, which identifies a subset of patients with poor outcome. Our data suggest that in future phase 3 trials, LDH should be taken into account for the stratification of patients. Furthermore, elevated baseline serum LDH should be included in the current criteria (i.e. poor risk cytogenetics, high plasma cell labeling index) which are being used to characterize high risk myeloma.

Disclosures:
No relevant conflicts of interest to declare.