The Impact of Time from Diagnosis to Initiation of Chemotherapy on Survival of Patients with Diffuse Large B-Cell Lymphoma in the Veteran`s Health Administration

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin`s lymphoma in adults. Although most patients present with advanced disease, cure rates surpass 60% with R-CHOP immunochemotherapy. Those failing initial treatments tend to have poor outcomes (PMID: 33657296). Currently, the optimal time from diagnosis to treatment (TDT) is unknown, however, previous clinical trials in breast cancer and colorectal cancer have revealed that earlier initiation of treatment leads to improved clinical outcomes. There are no standard TDT guidelines for DLBCL and data shows a wide median range (14 - 37 days) in different health care systems (PMID: 33531642). Our retrospective study explores the impact of TDT on outcomes of patients treated within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States providing care to over 9 million veterans.

Methods Medical records of 5199 veterans who were patients in the VHA and diagnosed with some form of lymphoma between January 1, 2011, and December 31, 2019, were randomly selected and reviewed. Patients with a diagnosis of DLBCL were included. Those with primary central nervous system (CNS) lymphoma, who had all the workup and treatment outside the VHA, or that were not treated with chemotherapy were excluded. We analyzed TDT, defined as the number of days from the date of pathology results to the date of initiation of treatment, and divided these into five groups: ≤ 1 week, 1-3 weeks, 3-5 weeks, 5-7 weeks, and ≥ 7 weeks. Very high-risk patients defined as those with TDT ≤ 1 week, IPI score of 3-5, and hospitalized at the start of treatment were analyzed separately. Overall survival (OS) was defined as the period between the date of diagnosis and the date of death from any cause, while progression-free survival (PFS) was determined as the time from the first treatment dose to radiographic or clinical progression or death from any cause. OS and PFS were estimated using the Kaplan-Meier method and compared using the Wilcoxon-Mann-Whitney test.

Results A total of 2448 patients were included in this study. Most patients were males (96.6%) with a median age of 68 years (table 1). The median TDT was 19 days, the median PFS was 46.8 months, and the median OS was 54.1 months. 23.6% of patients had a TDT of ≤1 week, 31.2% of 1-3 weeks, 20.2% of 3-5 weeks, 11.2% of 5-7 weeks, and 13.8% of ≥ 7 weeks; the median PFS was 31.9 months, 49.9 months, 52.9 months, 51.2 months, and 49.2 months; the median OS was 40.3 months, 56.4 months, 59.2 months, 55.8 months, and 54.2 months; and the 2-year OS was 60.2%, 71.6%, 77.3%, 82.8%, and 76.3%, respectively. When comparing the 2-year OS of the TDT ≤ 1 week group to all other groups individually, there was a significant difference favoring survival in any of the TDT >1 week groups (p<0.001). There was not, however, a significant difference when comparing the 1-3 weeks, 3-5 weeks, 5-7 weeks, and ≥ 7 weeks groups. The median PFS in the high-risk group was 7.2 months and the median OS was 11.2 months (table 2).

Conclusion This retrospective cohort study of 2448 patients with DLBCL is a continuation of our group's work (Williams et al, ASH 2020) and one of the largest studies evaluating the impact of TDT on outcomes. We demonstrated that OS and PFS were significantly lower in the ≤ 1 week group. Very high-risk patients had at least a fourfold decrease in OS and PFS compared to other groups. Patients with more adverse prognostic factors at diagnosis were more likely to be hospitalized and start treatment earlier. This study has limitations. Electronic Health Records data are created for patient care, not for research, and might have missing prognostic information. Besides, the VHA database contains a predominantly elderly, white, male population which might not be generalizable to non-VHA settings. Further studies are needed to determine the optimal TDT based on risk stratification in patients with DLBCL.

Nooruddin:Astrazeneca: Research Funding.