PROGNOSTIC VALUE OF THE INTERVAL BETWEEN RELAPSE AND THERAPY INITIATION IN DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS. ANALYSIS FROM THE CZECH LYMPHOMA STUDY GROUP DATABASE

Introduction: Patients with relapsed/progressed diffuse large B-cell lymphoma (rDLBCL) survive globally with median 12 months since relapse and majority of deaths is attributed to lymphoma. There is urgent need of efficient therapy for rDLBCL, but clinical trials cannot find efficient therapy up to now. Regardless the selection bias of inclusion/exclusion criteria in clinical trials, time to therapy initiation seems to be a critical point for the trial enrollment. Methods: As a data source for this retrospective analysis, the CLSG (Czech Lymphoma Study Group; Govtrial NT 03199066) database was used. Patients with the first relapse/progression of DLBCL (initial diagnosis 2000-2017) and without CNS involvement were included. The date of relapse was defined as the first documented manifestation (clinical symptoms, radiological finding or the date of biopsy confirming DLBCL). According to time between diagnosis of relapse and start of therapy, patients were divided into three subgroups: 1) <7 days, 2) 7-21 days, and 3) ≥21 days, and the comparison of overall survival (OS) was carried out. Results: Totally, 587 patients with DLBCL relapsed with median 12.8 months (range; 1.6 to 152.3) since diagnosis, 304/587 (51.8%) were males, median age was 67 yrs (range 22-95) at the relapse, 351/587 (49.9%) patients had stage III/ IV, bone infiltration was found in 51/587 (8.7%) cases. B-symptoms appeared in 140/587 (23.9%) cases, ECOG>2 showed 61/587 (10.4%) and bulky disease (≥7.5cm) 129/587 (22%) patients. LDH>norm was present in 387/587 (65.9%) cases. First line systemic therapy was administered in 98% patients, the most frequent chemotherapy backbone was CHOP (70%), anti-CD20 was given to 84% patients (including 99% of rituximab). The therapy of rDLBCL was based on systemic immuno/chemotherapy in 81.9% of patients (40% platinum-based regimen). Median time between diagnosis of rDLBCL and therapy start was 20 days (1-851 days), 136 pts (23.2%) initiated therapy in <7 days, 166 (28.2%) pts between 7-21days, and 285 (48.6%) ≥21 days. Shorter interval between relapse and treatment was associated with shorter 5-year OS (17.4% vs. 20.5% vs. 42.2%; p<0.001). Subgroups with time to therapy intervals <7 days vs. ≥ 21 days showed significant differences in clinical and laboratory parameters: B-symptoms (32.8% vs. 18.6%; p.015), limited stage I/ II (31.1% vs. 44.6%; p.031), ECOG ≥3 (19.7% vs. 5%; p.001), bulky disease ≥ 7.5cm (40.2% vs. 19.6%; p.001), elevated LDH (80.8% vs. 58.9%; p.002). Conclusions: The short time between relapse/progression and therapy initiation in rDLBCL is associated with significantly shorter OS and mirrors real clinical behavior of DLBCL represented by worse clinical and laboratory parameters. Unfortunately, this high-risk proportion of patients requiring urgent therapy (< 7 days; 23%) usually fails to enter into majority of clinical trials. Keywords: diffuse large B-cell lymphoma (DLBCL); immunochemotherapy; prognostic indices.