Clinical Outcomes of Newly Diagnosed Multiple Myeloma Patients with Elevated Lactate Dehydrogenase Who Underwent Autologous Hematopoietic Stem Cell Transplantation

Abstract

Background Multiple Myeloma (MM) is a malignant disorder of clonal plasma cells. Elevated Lactate Dehydrogenase (LDH) has been shown to be an independent prognostic marker associated with shorter survival. Methods Utilizing data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass database, we identified patients with baseline LDH values (>4.68 microkatals/liter). We compared baseline characteristics and outcomes with autologous stem cell transplant (ASCT), based on LDH as categorical variable. Results We identified 871 patients with NDMM who had baseline LDH values. 385 patients underwent ASCT (High LDH N=44; Normal LDH N=341). Those with high LDH had an inferior OS when compared with those with normal LDH (median OS 800.5 vs 878.8 days, p=0.019). Of the 44 patients with high LDH who underwent ASCT, median age was 60 years and ECOG performance status was 1. 61.36% were females, 77% were Caucasian, 11% were African American. Induction therapy consisted of 4 drugs or more in 16%, 3 drugs in 61%, and 2 drugs in 23%. Bortezomib and immune modulating agents (IMIDS) were combined in 72%. In those who did not receive an IMID, a bortezomib-based induction was used in 16% and carfilzomib-based induction was used in 11%. 93.18% underwent transplant in the consolidative setting with a median time to transplant was 178 days. 21 of the 44 patients (47.72%) received post-transplant maintenance. 10/21(48%) patients received triplet, 8/21 (38%) patients received lenalidomide alone. The median duration of maintenance was 217 days. Of the 341 patients with normal LDH who underwent ASCT, the median age was age 61 years, ECOG performance status was 1. 41.34% were females, 79% were Caucasian, 13% African American. Induction therapy consisted of 4 drugs in 8%, 3 drugs in 64%, 2 drugs in 24%. Combined Bortezomib-IMID in 76.24%, carfilzomib-IMID based therapy in 6%, and bortezomib-non-IMID based in 9.67%. 94.7% underwent an upfront consolidative with median time to transplant 164 days. Post-transplant maintenance was given in 213/341 (62.4%) of patients, in whom triplet therapy was given to 41/213 (19.2%), doublet therapy to 34/213 (16%), 130/213 (61%) received single agent. Median duration of maintenance 266 days. There was no statistically significant difference in race, performance status, drug class and number of drugs used in induction therapy, time to transplant, whether or not patients received maintenance as well as maintenance duration between the groups when stratified by LDH. Female gender was enriched in the high LDH group (p=0.009). Conclusion Elevated LDH was confirmed as a poor prognostic factor in MMRF CoMMpass cohort. ASCT did not abrogate the poor prognosis associated with high LDH. Since clinical outcomes remain poor despite the use of novel effective therapies and early consolidation with AHCT in patients with high baseline LDH, this group represents an unmet need for alternative therapy.