Presence of Circulating Lymphoma Cells May Be Associated With Worse Survival Outcomes for Newly Diagnosed Patients With DLBCL

Presence of circulating lymphoma cells (CL) at time of diagnosis of de novo diffuse large B-cell lymphoma (DLBCL) was associated with inferior survival outcomes compared to patients without CL, according to a retrospective study published in the Journal of Hematology & Oncology.

Previous evaluation of circulating lymphoma cells (CL) in peripheral blood (PB) among patients with advanced stage DLBCL has been limited. To address this gap, researchers conducted a retrospective cohort study to determine the prognostic impact of CL at time of diagnosis in patients with newly diagnosed DLBCL.

Among eligible patients who all previously received anthracycline-based chemotherapy, PB immunophenotyping was conducted by flow cytometry at diagnosis. Matching of actual or expected B-cell immunophenotype of DLBCL in detectable kappa or lambda-restricted B-cells defined CL among patients. Peripheral smears with hematopathologist review were used to determine flow findings at time of diagnosis. Patients were stratified by CL status at time of diagnosis as either CL+ or CL-.

The primary end point was progression-free survival (PFS) and secondary end points were group comparisons of overall survival (OS) and diagnosis-to-treatment interval (DTI). Overall, 588 patients with newly diagnosed DLBCL were included in the study, of which 14.5% (n = 85) were CL+. The median age of enrolled patients was 70 years, the majority of patients had disease at stage 3 to 4 (92%), and almost half had B-symptoms (49%). Among all patients, overall response rate (ORR) was 86% and complete response rate (CRR) was 73%. The median PFS was 7.35 years (95% confidence interval [CI], 6.18 to 8.49) and OS 9.8 years (95% CI, 9.1 to 10.4).

Between groups, patients who were CL- had higher ORR (87% vs 78%, P =. 02) and CRR (75 vs 59, P < .01) than patients who were CL-. Additionally, median PFS (7.92 vs 1.7, P <. 0001) and OS (10.04 vs 7.82, P = .0019) were higher among patients who were CL- than patients who were CL+. Lower PFS (HR, 2.04; 95% CI, 1.47-2.84, p<.001) and OS (HR, 1.61; 95% CI, 1.1 to 2.36, P <. 001) remained associated with CL+ even after adjustment for associated risk factors.

Additional sensitivity analysis results demonstrated no statistical difference in type of first-line therapy in either cohort. However, patients who received intensive-induction chemotherapy and were CL+ had an increased risk for poor OS (HR, 2.32; 95% CI, 1.4 to 3.84).

“In this largest study-to-date evaluating the impact of CL on outcomes in patients with newly diagnosed de novo DLBCL, we found that presence of CL at diagnosis was associated with inferior response rates and survival compared to those without CL,” the researchers concluded. “Given the relevance associated with the presence of CL, clinicians should consider checking PB flow at diagnosis in all newly diagnosed patients with DLBCL,” they added.

Source:

Chowdhury SM, Subodh Bhatta, Voorhees TJ, et al. Impact of circulating lymphoma cells at diagnosis on outcomes in patients with newly diagnosed de novo diffuse large B-cell lymphoma. Journal of Hematology & Oncology. Published online January 5, 2025. doi: 10.1186/s13045-024-01658-y