The most prevalent B-cell non-Hodgkin lymphoma is diffuse large B-cell lymphoma (DLBCL). Various prognostic factors were known, including the revised international prognostic index (R-IPI), MYC/BCL2 overexpression by IHC, MYC/BCL2 and/or BCL6 rearrangement (double hit/triple hit lymphomas [DHL/THL]), CD5 expression, and metabolic tumor volume. These risk stratification tools were under development. However, the significance of circulating lymphoma (CL) in individuals with DLBCL at diagnosis was largely unclear outside of case reports and limited case studies. As a result, researchers aimed to assess how CL at diagnosis affected patients with DLBCL outcomes.

The participants in the single-center, retrospective cohort analysis of DLBCL patients treated at Ohio State University had to be ≥18 and had their diagnosis confirmed by flow cytometry between 2010 and 21. Patients were divided into two groups, CL+ and CL-, based on whether the flow cytometry findings were positive or negative. PFS (progression-free survival) was the primary goal, while OS (overall survival) in the CL+ and CL- groups was the secondary endpoint. PFS was determined by censoring the most recent clinical evaluation and measuring the period of time from the commencement of first-line treatment until lymphoma relapse/progression or death from any cause. The OS period was measured from the beginning of first-line treatment until the patient’s passing or last follow-up. R-CHOP and intense induction therapy (R-EPOCH, R-hyperCVAD, and R-CODOX-M/R-IVAC) were the two groups assigned to the first-line treatment.

At diagnosis, 30 (17%) of the 181 eligible patients with newly diagnosed DLBCL showed detectable CL, while 151 (83%) did not. In comparison to the CL- group, patients in the CL+ group had a higher median age (66 vs 64 years), more advanced disease stage (97% vs 83%), and a higher R-IPI score of 3-5 (89% vs 62%). Gender, race, ECOG performance status, bulky illness, presence of B symptoms, cell of origin, synchronous central nervous system (CNS) involvement, DHL/THL, and first-line treatment were equally distributed amongst the two groups. In the CL+ group, the median PFS was 4.2 years (95% CI=0.9-not reached [NR]), while in the CL- group, it was 10.9 years (95% CI=4.8-NR) (P=0.20). Between the CL+ and CL- groups of patients receiving R-CHOP treatment, the median PFS was not statistically different (median PFS NR versus 10.9 years, respectively, P=0.99). However, as compared to the CL+ group, the CL- group receiving extensive induction treatment had a considerably longer median PFS (median PFS 1.8 years versus NR, respectively, P=0.04). There was no difference in PFS between the CL+ and CL- groups (HR=1.48, 95%CI=0.77-2.85, P=0.24) after characteristics associated with PFS in multivariable cox regression (gender, R-IPI, first-line treatment, synchronous CNS involvement, and DHL/THL) were taken into account. In the CL+ group, the median OS was 4.2 years (95%CI=1.7-NR), while in the CL- group, it was NR (P=0.05, Figure 2). There was no difference in OS between the CL+ and CL- groups (HR=1.85, 95%CI=0.90-3.79, P=0.09) when characteristics associated with PFS in multivariable cox regression (gender, R-IPI, first-line treatment, synchronous CNS involvement, and DHL/THL) were taken into account.

The outcomes of patients with CL+ and CL- groups in newly diagnosed DLBCL WERE compared for the first time in the study. They discovered that CL at diagnosis was not associated with a shorter PFS but did tend towards a worse OS in the largest study to date evaluating the prognostic relevance of CL in patients with DLBCL. At first relapse, experimental and cellular therapies should be given priority for the CL+ group because they represent a potentially high-risk patient population. Future prospective studies ought to test for CL and confirm the results of the study.

Reference: ash.confex.com/ash/2022/webprogram/Paper166988.html