β2-microglobulin is superior to lactate dehydrogenase and bulky disease for risk stratification in diffuse large...

The International Prognostic Index (IPI) is the classical assessment tool to evaluate prognosis of diffuse large B cell lymphoma (DLBCL). Although the IPI is simple, reproducible, well validated and widely utilized, it is not entirely accurate in some patients with DLBCL. Recently, it was reported that a subgroup of high-risk DLBCL patients with IPI score 1 or 2 can be identified by bulky disease and high lactate dehydrogenase (LDH) levels. Such classification of high-risk DLBCL has been used in new clinical trials. We analyzed out cohort database to validate such a sub-classification and further evaluated subdivision by serum β2-microglobulin levels. We retrieved the list of patients with new diagnosis of DLBCL between 2015 and 2019 from the Chang Gung Memorial Hospital in Linkou. Consecutive cases were enrolled without a pre-set sample size assessment. For each patient, the IPI was calculated according to published literature. Patients with an IPI score of 1 and 2 were included for this analysis. High-risk DLBCL was defined as bulky tumors (> 7 cm) or high LDH levels (> 1.3-fold upper limit). Serum β2-microglobulin levels were measured in the clinical laboratory. Analyses were done by comparing patients with or without high-risk features as well as patients with or without high β2-microglobulin levels (≥ 3000 µg/L). In 523 patients with DLBCL, 238 had an IPI score of 1-2, and 234 (115 male and 119 female) had sufficient data for high-risk DLBCL sub-classification. The median age was 64 years (range 26 to 90 years). Blood level of β2-microglobulin correlated with that of LDH (r2 = 0.03, p = 0.0136). There was no difference in β2-microglobulin levels between patients with and without bulky tumors (p = 0.3573). Using LDH > 1.3-fold upper limit as the cutoff, patients with high LDH had significantly higher levels of β2-microglobulin (p = 0.0096). Sixty-seven patients had high-risk features, defined by high LDH or bulky disease. These patients have significantly higher β2-microglobulin levels (p = 0.0173). However, in clinical outcome, high-risk and low-risk DLBCL do not differ significantly in progression-free survival (p = 0.8794) or overall survival (p = 0.4464). Using 3000 µg/L as a cutoff, patients with high β2-microglobulin levels had significantly shorter progression-free survival (p = 0.0183) than those with low levels. The difference in overall survival between high and low-level β2-microglobulin did not reach statistical significance (p = 0.2044). Our experience suggests the high-risk sub-classification based on LDH and bulky disease among patients with an IPI score of 1 or 2 does not correlate with clinical outcomes. In contrast, high levels of β2-microglobulin may help identify a sub-group of high-risk patients. This biomarker may be helpful in refining treatment plans or designing future clinical trials.