The Prognostic Impact of Inflammatory Factors for Survival in Patients with Newly Diagnosed Multiple Myeloma Who Were Treated with Thalidomide Containing Induction Chemotherapy Underwent Autologous Stem Cell Transplantation
Authors: Kim Cheolsu , Lee Ho Sup , Kim Yang Soo , Min Chang-Ki , Lee Je-Jung , Kim Kihyun , Yoon Dok Hyun , Eom Hyeon Seok , Lee Hyewon , Lee Won Sik , Shin Ho-Jin , Lee Ji Hyun , Park Yong , Jo Jae-Cheol , Do Young Rok , Mun Yeung-Chul 
Published: October 2019

Abstract
Background: Many prognostic factors have been studied with the development of treatments for multiple myeloma (MM). Serologic inflammatory markers, such as serum beta2-microglobulin (B2MG), albumin, absolute lymphocyte count (ALC), C-reactive protein (CRP), lactate dehydrogenase (LDH), and serum ferritin level, which are easily tested in patients to determine disease status, have been reported to be correlated with prognosis in many studies. Therefore, the purpose of this study is to estimate the correlation between the frequency of the combined inflammatory parameters of ALC, LDH, B2MG, albumin, CRP, and ferritin and the prognosis for survival in patients with MM treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT).
Methods: Data from patients at 13 university hospitals in South Korea between December 2005 and May 2013 were collected retrospectively. The patients were those who had been treated with thalidomide-containing chemotherapy and then underwent ASCT. An inflammatory score was determined for each inflammatory parameter, where an ALC level less than 1000/L, a B2MG level greater than 3.5 mg/L, a serum albumin level less than 3.5 g/dL and an LDH level greater than 450 IU/L were each assigned a score of 1 point, and the sum of these points was used as the total inflammatory score ranging from 0 to 4 points.
Results: The median age of the 232 patients was 57 years (range, 33-82 years) and the male to female ratio was 1.09:1. The achieved response rates before and after ASCT were as follows: complete response (CR) or stringent CR (sCR) in 81 (34.9%) and 142 (60.2%) patients, very good partial response (VGPR) in 61 (26.3%) and 47 (20.3%), partial response (PR) in 79 (34.1%) and 32 (13.8%), and < PR in 7 (3.1%) and 5 (2.3%). The reason for the higher overall response rate (ORR) in this study compared to other studies was that it included patients who were treated with thalidomide induction chemotherapy and who underwent ASCT. The median progression free survival (PFS) was 31.93 months (range, 25.116 – 38.750) and the median overall survival (OS) was not reached during the follow-up duration. In the univariate analysis, the following factors were associated with a greater than 3-year PFS: lower B2MG (< 3.5 mg/L vs. ≥ 3.5 mg/L; 49.7% vs. 40.4%, p=0.022), lower LDH (< 450 IU/L vs. ≥ 450 IU/L; 47.9% vs. 31.5%, p=0.009), lower cytogenetic risks (standard vs. intermediate vs. high; 51.4% vs 26.2% vs 52.7%, p=0.022) and a lower inflammatory score (< 2 vs. ≥ 2; 53.6% vs. 35.1%, p=0.004). The following factors were associated with a greater than 3-year OS (Table 2): higher hemoglobin level (< 10 g/dL vs. ≥ 10 g/dL; 81.0% vs. 92.8%, p=0.042), higher platelet count (<100×109/L vs. ≥ 100×109/L; 48.5% vs. 89.5%, p=0.003), lower B2MG (< 3.5 mg/L vs. ≥ 3.5 mg/L; 95.2% vs. 81.1%, p=0.003), lower LDH (<450 IU/L vs. ≥ 450 IU/L, 91.6 vs. 69.5, p=0.003), lower cytogenetic risk (standard vs. intermediate vs. high; 89.1% vs. 81.7% vs. 81.0%, p=0.014), lower ISS (I, II, and III; 95.2%, 90.3%, and 78.3%, respectively; p=0.024) and a lower inflammatory score (<2 vs. ≥ 2; 95.1% vs. 77.1%, p<0.001). In the multivariate analysis, inflammatory score (<2) was the only independent prognostic factor for superior PFS (RR 0.618, 95% C.I. 0.409-0.933, p=0.022), and platelet count greater than 100×109/L as well as an inflammatory score less than 2 were independent prognostic factors for superior OS (RR 7.856, 95% C.I. 2.502-24.670, p<0.001 and RR 0.216, 95% C.I. 0.067-0.696, p=0.010, respectively).
Conclusion:patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed a significantly shorter survival compared to patients with less than two combined inflammatory factors, and these results might be helpful to predict prognosis in patients with MM. In the future, further prospective studies will be needed to confirm the correlations between prognosis and inflammatory factors including CRP, ferritin, and other cytokines in patients with MM treated with novel agents.

Disclosures
No relevant conflicts of interest to declare.