PF320 VENOUS THROMBOSIS AND BASELINE C‐REACTIVE PROTEIN ARE INDEPENDENT PROGNOSTIC MARKERS IN DIFFUSE LARGE B‐CELL LYMPHOMA AND IDENTIFY A GROUP OF PATIENTS WITH SIGNIFICANTLY INFERIOR OUTCOMES
Authors: Grech M. , Farrugia D. , Camilleri D.‐J. , Gatt A. 
Published: June 2019

Background:

The association between inflammation and cancer has been well described. C‐reactive protein (CRP) is one of the most commonly utilised inflammatory markers in clinical practice. Many studies have demonstrated that elevated CRP is an important prognostic factor in different types of cancer. Venous thromboembolism (VTE) is a common complication in patients with cancer and has also been associated with worse outcomes.

Aims:

The aim of our study is to verify whether the CRP at diagnosis and the presence of VTE are valid prognostic parameters in diffuse large B‐cell lymphoma (DLBCL).

Methods:

Data from patients with DLBCL treated with rituximab‐based chemotherapy between January 2008 and December 2018 were retrospectively evaluated. Only patients with CRP performed at baseline were included. Episodes of VTE confirmed by imaging studies that were present at diagnosis or occurred during initial therapy were identified. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to determine the best cut‐off value of CRP for survival. Kaplan‐Meier curves with log‐rank test and Cox regression were used to assess the impact of pre‐treatment CRP, VTE and other parameters on the overall survival (OS).

Results:

316 cases of DLBCL were identified during the study period; 16 patients (5.1%) were excluded because pre‐treatment CRP was not available. Three hundred patients were included in the study with a median follow‐up of 54.8 months (range 2.9–133.9 months) and median age of 66 years (range 18–97 years). One hundred and fifty‐two patients (50.7%) were female and 148 patients (49.3%) were male. The best cut‐off for CRP at diagnosis was 30 mg/L with an AUC of 0.72 (95% CI, 0.65–0.77, P < 0.001). Elevated CRP levels (>30 mg/L) were present in 159 patients (53.0%), while 141 patients (47.0%) had low CRP levels (≤30 mg/L). Thrombosis occurred in 12.7% of patients (39 events in 38 of 300 patients). Patients with a high CRP were more likely to have B symptoms (P < 0.001), Ann Arbor Stage III or IV disease (P = 0.007), bulky disease (P = 0.003), higher ECOG performance scores (P < 0.001), raised LDH levels (P < 0.001), more extra‐nodal areas involved (P < 0.001) and higher revised International Prognostic Index (R‐IPI) scores (P < 0.001). Patients with thrombosis were more likely to have Ann Arbor Stage III or IV disease (P = 0.005), bulky disease (P = 0.01), elevated baseline LDH (P = 0.002), elevated baseline CRP (P = 0.017) and higher R‐IPI scores (P = 0.03).

The OS at 5 years was 38% in patients with elevated baseline CRP and 74% in patients with low CRP (P < 0.001), while the 5‐year OS was 24% in patients with VTE and 59% in patients without VTE (P < 0.001). On multivariate analysis the baseline CRP (HR: 2.48 [95% CI: 1.65–3.73]; P < 0.001) and presence of VTE (HR: 2.17 [95% CI: 1.42–3.32]; P = 0.002) both retained prognostic significance for OS when controlling for the R‐IPI. Even though the prognostic impact of CRP and thrombosis was valid for the entire cohort, their significance was even more striking when present in the subgroup of patients with poor risk R‐IPI score, where the presence of both VTE and an elevated baseline CRP was associated with a median OS of only 3.3 months (P = 0.001).

Summary/Conclusion:

This study shows that baseline CRP and the presence of VTE are both independent predictors of worse OS in DLBCL. The combination of poor risk R‐IPI with elevated baseline CRP and venous thrombosis identifies a group of patients with particularly poor outcomes.

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