Use of the cumulative amount of serum-free light chains (sFLC) at diagnosis and PET2 for the early identification of high risk of treatment failure in Hodgkin lymphoma (cHL).

Abstract

8083 Background: Since early identification of patients (pts) at risk of failure is the mainstay of a risk-adapted therapy, we explored the prognostic impact of the sFLC assay in cHL, whose biology involves ongoing activation of polyclonal B-cells. Methods: Serum samples from 248 untreated cHL pts were tested by the Freelite assay. Median age was 32 yrs (r 15-85), males 47%, stages: I (5%), II (51%), III (17%), IV (27%); B-sympt. 60%, E-disease, 38%; bulky >10 cm, 44%; ESR > 65, 42%; IPS ≥3, 39%. Early unfavorable disease (GHLSG/ EORTC) was respectively found in 33% and 42% of cases. ABVD was given to 89% of pts. Results: Absolute FLC levels were summed into a sFLC(κ+λ) variable and ROC analysis indicated 57.1 mg/mL as the threshold to discriminate outcomes. CR rates were 96% and 67% for pts below and above the cutoff, respectively (p<.0001). Cox univariate analysis disclosed a HR of 16.70 (95% CI, 8.5-32.9) of events for sFLC(κ+λ) ≥ 57.1 mg/mL, by far higher than for PET2 positivity (HR 10.8), PS >1 (HR 4.2), IPS ≥3 (HR 2.8) and all other predictors (HR 0.54-2.4). In a multivariaye model only sFLC(κ+λ) and PET2 remained independent predictors. A dismal 8-yrs EFS characterized pts with sFLC(κ+λ) above threshold (20% vs 89%; Χ2 119, p<.0001). Pts with sFLC(κ+λ) below cutoff and a negative PET2 had an EFS of 93% as compared to 36% of those with sFLC(κ+λ) above cutoff or a positive PET2. Pts with sFLC(κ+λ) above cutoff and positive PET2, had the worse outcome with an EFS <10% and a median survival <12 mo.s (Χ2 65.4; p<.0001). sFLC assay was even more valuable in identifying poor risk pts within the early unfavorable category (5-yrs EFS <25%, Χ2 51 p<.0001). By immunoistochemistry small B cells and plasmacytoid lymphocytes were identified as the main source of sFLC in HL tissues while a strong sFLC uptake by mast cells was documented. Conclusions: A cumulative amount of sFLC ≥57.1 mg/mL, is the strongest independent predictor of failure in cHL. Combining sFLC(κ+λ) and PET2 outcomes can timely discriminate poor risk pts subsets, who may benefit from upfront treatment escalation or early salvage. Our data also support that sFLC might endorse immunobiologic activities relevant to cHL pathobiology.