The Prognostic Significance of Serum β₂- Microglobulin Levels (sβ₂m) in Diffuse Large B-Cell Lymphoma (DLBCL)

INTRODUCTION:The International Prognostic Index (IPI) is the standard-but not optimal- tool for prognostication in DLBCL. Sβ₂m levels is a well- established prognostic factor for several hematologic malignancies. Its prognostic role has been demonstrated in several studies in DLBCL using various cutoffs, but has not been included current in prognostic systems. We aimed to investigate the prognostic significance of sβ₂m levels in a large series of homogenously treated DLBCL patients in the rituximab era.

Patients and Methods: We analyzed 1129 patients with DLBCL treated with R-CHOP or similar regimens and selected based on the availability of pretreatment sβ₂m levels in Hellenic centers. Sβ₂m levels were analyzed as absolute value measured in mg/L or as the ratio of the observed value to the upper normal limit of the respective laboratory. Sβ₂m levels were analyzed as continuous variable in relation to other baseline features. The analysis of the prognostic significance of sβ₂mand sβ₂m ratio was performed using quartiles (Q1-Q4) or the median value. Freedom From Progression (FFP) was defined as time between treatment initiation and treatment failure (toxic death, primary refractoriness, PR with switch to alternative chemotherapy or relapse); deaths of unrelated causes were censored.

Results:The median absolute sβ₂m levels were 3.00 mg/L [interquartile range (IQR)2.12-4.53, range 1.05-46.30] and the median sβ₂m ratio was 1.33 (IQR 0.95-2.00, range 0.30-20.60). Both sβ₂m and sβ₂mratio correlated strongly with all baseline features (p<0.001).Univariate Analysis: FFP was significantly worse in patients with high sβ₂m (≥median of 3 mg/L) with 2-year FFP of 62.9% vs 84.9% (p<0.001). A gradual worsening of FFP was observed from Q1 to Q4 with 2-year FFP rates of 91.9%, 77.7%, 70.0% and 55.6% (p<0.001). Similar results of somewhat lower magnitude were observed with sβ₂mratio, with 2-year FFP rates of 91.2%, 78.9%, 72.8% and 56.2% for Q1-Q4 respectively (p<0.001). The IPI was strongly predictive of FFP, as expected (p<0.001).Multivariate Analysis: When sβ₂m quartiles were analyzed together with IPI (0-1 vs 2 vs 3 vs 4-5), in terms of FFP, both factors had independent prognostic significance (p<0.001 for IPI and p=0.001 for sβ₂m quartiles). Adjusted for IPI, the hazard ratio for Q4, Q3, and Q2 versus Q1 were 2.40, 1.70, and 1.62 (all p-values<0.05). The sβ₂mratio was also independent from IPI (hazard ratios for Q4,Q3 and Q2 versus Q1 were 2.88, 2.03 and 2.12).

Conclusion: Higher sβ₂m Levels was a significant independent predictor of FFP in DLBCL, when adjusted for IPI. A cutoff of 3 mg/L appears reasonable irrespective of the lab reference values, as absolute values were marginally better predictor of FFP compared to values adjusted to the upper normal limit of each lab.

Triantafyllou:JANSSEN: Research Funding. Kyrtsonis:JANSSEN: Honoraria; GSK: Honoraria; TAKEDA: Honoraria; AMGEN: Honoraria. Papadaki:x4 pharmaceutical company: Honoraria, Membership on an entity's Board of Directors or advisory committees. Angelopoulou:Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.