MM-315: Impact of Stratification of Levels of Serum Lactate Dehydrogenase (LDH) at Diagnosis on Overall Survival (OS) in Newly Diagnosed Multiple Myeloma (NDMM)

Abstract

Context Elevated serum LDH level is an adverse prognostic factor in NDMM. Quantitative serum LDH levels range from over the upper limit of normal (ULN) to levels 2- or more-fold higher than ULN. Objective The “normal versus elevated” classification of serum LDH level can fail to discriminate between different NDMM disease biology. Thus, we attempted to further stratify NDMM patients by their serum LDH level and determine the impact on OS outcomes. Design and Setting The cohort included patients diagnosed with NDMM from the Mayo Clinic, Rochester, from 2003 to 2017, treated with novel agent induction therapy with measured serum LDH levels at the time of diagnosis. Patients The cohort consists of 1,196 NDMM patients with median age of 65 (22–95) years. R-ISS classification was available for 968 patients and is distributed as follows: 210 (22%) stage 1, 639 (66%) stage 2, and 119 (12%) stage 3. Cytogenetic risk data was available for 970 patients: 215 (22%) high-risk and 755 (78%) standard-risk. Main Outcome Measures The serum LDH levels were stratified into three levels: normal (LDH < 222 U/L), elevated (LDH 223–444 U/L), and very elevated (LDH >444 U/L). Survival analysis was performed using the Kaplan–Meier method and compared via Wilcoxon method. Results Median serum LDH level was 162 U/L (3–1260), and an elevated LDH was present in 199 patients (17%). Median OS for patients with normal (N = 997; 83%), elevated (N = 170; 13%), and very elevated (N = 29; 3%) LDH levels were 76 months, 57 months, and 23 months respectively (P < 0.001). Impact of LDH levels on OS by R-ISS stage and cytogenetic risk was analyzed, and regardless of R-ISS stage/cytogenetic risk, very elevated patients had significantly smaller median OS (discrepancy ranging from 19 months [R-ISS stage 3] to 36 months [R-ISS stage 2] than elevated patients (P ≤ 0.0022 for all classifications). Conclusion A small subset (3%) of NDMM have very elevated LDH levels that confer exceptionally poor OS, irrespective of R-ISS stage and cytogenetic risk. Future studies determining disease biology responsible for such poor OS outcomes are warranted. Acknowledgments Research was supported by the National Cancer Institute [Grant Number CA254961], the Helen Diller Family Foundation, and the Marion Schwartz Foundation for Multiple Myeloma. Elevated serum LDH level is an adverse prognostic factor in NDMM. Quantitative serum LDH levels range from over the upper limit of normal (ULN) to levels 2- or more-fold higher than ULN. The “normal versus elevated” classification of serum LDH level can fail to discriminate between different NDMM disease biology. Thus, we attempted to further stratify NDMM patients by their serum LDH level and determine the impact on OS outcomes. The cohort included patients diagnosed with NDMM from the Mayo Clinic, Rochester, from 2003 to 2017, treated with novel agent induction therapy with measured serum LDH levels at the time of diagnosis. The cohort consists of 1,196 NDMM patients with median age of 65 (22–95) years. R-ISS classification was available for 968 patients and is distributed as follows: 210 (22%) stage 1, 639 (66%) stage 2, and 119 (12%) stage 3. Cytogenetic risk data was available for 970 patients: 215 (22%) high-risk and 755 (78%) standard-risk. The serum LDH levels were stratified into three levels: normal (LDH < 222 U/L), elevated (LDH 223–444 U/L), and very elevated (LDH >444 U/L). Survival analysis was performed using the Kaplan–Meier method and compared via Wilcoxon method. Median serum LDH level was 162 U/L (3–1260), and an elevated LDH was present in 199 patients (17%). Median OS for patients with normal (N = 997; 83%), elevated (N = 170; 13%), and very elevated (N = 29; 3%) LDH levels were 76 months, 57 months, and 23 months respectively (P < 0.001). Impact of LDH levels on OS by R-ISS stage and cytogenetic risk was analyzed, and regardless of R-ISS stage/cytogenetic risk, very elevated patients had significantly smaller median OS (discrepancy ranging from 19 months [R-ISS stage 3] to 36 months [R-ISS stage 2] than elevated patients (P ≤ 0.0022 for all classifications). A small subset (3%) of NDMM have very elevated LDH levels that confer exceptionally poor OS, irrespective of R-ISS stage and cytogenetic risk. Future studies determining disease biology responsible for such poor OS outcomes are warranted.