Impact of circulating lymphoma cells at diagnosis on outcomes in patients with newly diagnosed de novo diffuse large B-cell lymphoma.

in Journal of hematology & oncology by Sayan Mullick Chowdhury, Subodh Bhatta, Timothy J Voorhees, Kaitlin Annunzio, David A Bond, Yazeed Sawalha, Audrey Sigmund, Walter Hanel, Lalit Sehgal, Lapo Alinari, Robert Baiocchi, Kami Maddocks, Beth Christian, Dan Jones, Narendranath Epperla

TLDR

  • The study found that circulating lymphoma cells at diagnosis are associated with inferior progression-free survival and overall survival in diffuse large B-cell lymphoma patients.
  • Clinicians should consider checking peripheral blood flow at diagnosis to determine the presence of circulating lymphoma cells.

Abstract

Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma rarely presents with circulating lymphoma cells (CL) at diagnosis. Previous studies were limited by small sample size precluding robust analysis. Hence, we evaluated the prognostic relevance of CL cells in newly diagnosed DLBCL patients. Based on peripheral blood (PB) immunophenotyping, patients were grouped into CL + and CL-. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of DLBCL. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and diagnosis-to-treatment interval (DTI). Among the 1266 patients with DLBCL, 621 had PB flow at diagnosis, and after excluding patients not meeting eligibility criteria, 588 cases remained. Among these, 85 (15%) were CL + and 503 were CL- (85%). Patients in CL + group were younger (67 vs. 70 years, p = 0.03) with a higher proportion of non-bulky disease (85% vs. 56%, p < 0.0001), normal albumin (79% vs. 54%, p < 0.0001), and MYC/BCL2 and/or BCL6 rearrangements (18% vs. 7%, p = 0.003) compared to the CL - group. Patients with CL at diagnosis had significantly inferior PFS and OS compared with those without CL. After adjusting for factors associated with inferior PFS and OS in univariable analysis, presence of CL remained significantly associated with inferior PFS (HR = 2.04, 95%CI = 1.47-2.84, p < 0.0001) and OS (HR = 1.61, 95%CI = 1.1-2.36, p = 0.01), respectively. There was no significant difference in DTI between the two groups. Given the prognostic relevance associated with presence of CL, clinicians should consider checking PB flow at diagnosis in all newly diagnosed DLBCL patients.

Overview

  • The study evaluated the prognostic relevance of circulating lymphoma cells (CL) in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients.
  • Patients were grouped into CL+ and CL- based on peripheral blood immunophenotyping, and the primary endpoint was progression-free survival (PFS).
  • The study included 588 DLBCL patients with PB flow at diagnosis, and 85 (15%) were CL+ and 503 were CL- (85%).

Comparative Analysis & Findings

  • Patients in the CL+ group were younger, had a higher proportion of non-bulky disease, normal albumin levels, and were more likely to have MYC/BCL2 and/or BCL6 rearrangements compared to the CL- group.
  • Patients with CL at diagnosis had significantly inferior PFS and OS compared to those without CL.
  • Presence of CL remained significantly associated with inferior PFS and OS after adjusting for factors associated with inferior PFS and OS in univariable analysis.

Implications and Future Directions

  • Given the prognostic relevance of CL, clinicians should consider checking PB flow at diagnosis in all newly diagnosed DLBCL patients.
  • Future studies could investigate the use of PB flow as a predictive biomarker for DLBCL treatment and response.
  • Additional studies are needed to determine the impact of PB flow on patient outcomes and to explore potential therapeutic strategies targeting CL.
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