PF318 IMPORTANCE OF DIAGNOSIS‐TO‐TREATMENT INTERVAL IN NEWLY DIAGNOSED PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA
Authors: Yoshida M. , Nakaya Y. , Tsutsumi M. , Fuseya H. , Horiuchi M. , Yoshimura T. , Hayashi Y. , Nakao T. , Yamane T. 
Published: June 2019

Background:

Treatment of patients with malignancy sometimes delay due to various reasons (e.g., additional examination, enrollment in clinical trial). Several studies revealed that an influence of diagnosis‐to‐treatment interval (DTI) on outcomes differs depending on the type of malignancy. But, it is not well understood how delayed treatment affects outcomes in diffuse large B‐cell lymphoma (DLBCL).

Aims:

In the present study, we evaluated the influence of DTI and other parameters on clinical outcomes in newly diagnosed patients with DLBCL.

Methods:

We conducted a retrospective analysis using a database at our hospital. Patients were eligible if aged 20 years or older, newly diagnosed with DLBCL between April 2007 and March 2017, and received CHOP or dose‐reduced CHOP‐like regimen with or without rituximab. The primary endpoint of this study was overall survival (OS). The OS was defined as the time from diagnosis to the last visit with the patient or death from any cause. DTI was defined as the time from pathological diagnosis to the initiation of treatment.

Results:

A total of 199 patients were identified, with a median age of 70 years (range 28–87), 81% >60 years, 51% male, 68% Stage III/IV, 60% IPI high–int/high and 16% diagnosed in other facilities. A median DTI was 22 days (range 0–393). 48% were treated with CHOP, 52% dose‐reduced CHOP‐like regimen and 94% were combined with rituximab. Median observation time was 1091 days (range 31–3951). Short DTI (0–22 days) was associated with clinical factors such as older age, poorer performance status (PS), B symptom, lower serum albumin, elevated LDH, higher Ann Arbor stage, extranodal lesion, and higher IPI. Sex, facility of initial diagnosis, bulky lesion and treatment regimen were not associated with DTI.

At five years, patients with short DTI (0–22 days) showed poorer OS (47.7% vs 79.0%; p < 0.001, figure 1). When we divided patients into 6 groups by week of DTI, shorter DTI (under 3 weeks) remained to be associated with poorer OS.

Univariate analysis showed the parameters negatively affecting OS were: shorter DTI (0–22 days) (p < 0.001), older age (p = 0.02), poorer PS (p < 0.001), extranodal lesion (p < 0.01), B symptom (p = 0.04), lower serum albumin (p < 0.001), elevated LDH (p = 0.02), higher Ann Arbor stage (p < 0.001), higher IPI score (p < 0.001), non‐use of rituximab (p < 0.001), dose‐reduced CHOP‐like regimen (p = 0.02).

On multivariate analysis, short DTI (0–22 days) (HR 2.03, 95% CI [1.18, 3.52], p = 0.01), high IPI score (HR 1.25, 95% CI [1.00, 1.55], p = 0.049) and non‐use of rituximab (HR 2.88, 95% CI [1.39, 5.96], p < 0.01) were revealed as independent factors affecting OS.

Summary/Conclusion:

In this study, we observed strong association between short DTI and poor OS in newly diagnosed patients with DLBCL. Although strong correlations of DTI with several adverse factors may affected this association, short DTI remained to be an independent prognostic factor by multivariate analysis. We speculate that patients with short DTI were judged to need urgent treatment because of disease aggressiveness which are not appropriately included in standard prognostic tools. In addition to well‐known prognostic factors, DTI should be considered when comparing outcomes of treatments in a clinical trial.

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