Modified Staging System for Patients with Waldenstrom's Macroglobulinemia in a Chinese Cohort
Authors: Chen Jia , Li Jian , Zhou Daobin , Cao Xinxin 
Published: December 2024

Waldenström macroglobulinemia (WM) has been recognized as a rare subtype of low-grade B-cell lymphoma. Although WM mostly has an indolent course and the prognosis has improved during the last decades, WM remains incurable and perpetually relapse and most patients succumb to disease progression. Prognostic parameters of WM have been reexamined and a modified staging system of WM (MSS-WM) has been formulated recently. However, the derivation and validation cohorts included predominantly patients from the USA and Europe Our aim was to provide evidence of MSS-WM for 294 symptomatic WM patients in Asia.

We identified 294 active WM patients diagnosed between January 2000 and December 2023 from the Department of Hematology, Peking Union Medical College Hospital, Beijing, China. All diagnoses were reviewed based on the 2003 diagnostic criteria in the Second International Workshop on WM. Prognosis stratification was analyzed based on the MSS-WM, and compared with the 2009 prognostic scoring system for WM (IPSS-WM) and the 2019 revised international prognostic scoring system (rIPSS-WM). Overall survival (OS) was defined as the duration from diagnosis to death. The final follow-up date was May 31, 2024.

The median age was 64 years old, and the majority (71.4%) were male (Table S1). The median follow-up period was 48 months (0.3-241 months). Eighty-three patients died during the follow-up, with an estimated 5-year OS rate of 74.2%. On univariate analysis, all MSS-WM factors revealed independent prognostic impact with hazard ratios 2.44 for age 66-75 years old (P = 0.0003), 3.83 for age older than 75 years old (P &lt; 0.0001), 2.21 for albumin lower than 35g/L (P = 0.0017), 2.06 for lactate dehydrogenase higher than upper limit of normal (P = 0.0345) (Table 1). In the multivariate analysis of 236 patients, hazard ratios were 2.34 (P = 0.002) for age 66-76 years old, 2.7 (P = 0.0126) for age older than 75 years old, 1.94 (P = 0.0636) for albumin, 2.16 (P = 0.0636) for lactate dehydrogenase. Additionally, our results showed independent prognostic impact of beta-2 microglobulin higher than 4mg/L with hazard ratio 3.07 (P = 0.0002) and hemoglobin level with hazard ratio 2.10 (P = 0.0225), which is similar to the prognostic impact of beta-2 microglobulin in rIPSS-WM and hemoglobin in IPSS-WM, respectively.

According to MSS-WM in all 294 patients, 58 (19.7%) patients were classified as low risk (MSS-LR), 129 (43.9%) were low-intermediate risk (MSS-LIR), 76 (25.8%) were intermediate risk (MSS-IR), and 31 (10.5%) were high risk (MSS-HR). The 5-year OS rates were 89%, 84%, 52%, 52%, respectively (P &lt; 0.0001). The hazard ratios were 1.49 (95% CI, 0.71-3.53, P = 0.3205) for MSS-LIR versus MSS-LR, 3.99 (95% CI, 2.36-6.84, P &lt; 0.0001) for MSS-IR versus MSS-LIR, and 1.03 (95% CI, 0.54-1.87, P = 0.9182) for MSS-HR versus MSS-IR. In 233 patients available of IPSS-WM scores, 43 (18.5%) patients were classified as low risk, 102 (43.8%) were intermediate risk, and 88 (37.8%) were high risk. The 5-year OS rates were 88%, 84%, respectively (P = 0.0001). The rIPSS-WM scores were available in 236 patients. Among them, 30 (12.7%) patients were classified as very-low risk, 73 (30.9%) were low risk, 69 (29.2%) were intermediate risk, 46 (19.5%) were high risk, and 18 (7.6%) were very-high risk. The 5-year OS rates were 97%, 85%, 75%, 56%, and 40%, respectively (P &lt; 0.0001). The majority of patients had comparable performance between MSS-WM and IPSS-WM or rIPSS-WM. Based on IPSS-WM, a proportion of high risk patients (11/88, 12.5%) were down-staged in MSS-WM, and a few patients in low risk (2/43, 4.6%) and in intermediate risk group (3/102, 2.9%) were up-staged in MSS-WM. Based on rIPSS, a small fraction of rIPSS low risk patients (5/73, 6.8%) were up-staged as MSS-WM IR.

Our study provide evidence for the applicability of MSS-WM in a WM patient cohort in Aisa, and compared it with rIPSS-WM and IPSS-WM. MSS-WM, as a simplified model, demonstrated strong discrimination between patients with good and dismal prognosis, potentially facilitating its clinical use.