Prognostic markers in patients with chronic lymphocytic leukaemia on targeted therapy, chemoimmunotherapy with anti-CD20 monoclonal antibody: a systematic review and meta-analysis of prognostic factors

Abstract

Combination chemoimmunotherapy (CIT) consisting of anti-CD20 has improved the progression-free survival (PFS) and overall survival (OS) of patients with chronic lymphocytic leukaemia (CLL). We performed a comprehensive synthesis of prognostic factors in patients with CLL on combined CIT with anti-CD20 antibodies compared with standard chemotherapy alone or targeted therapy.We searched the MEDLINE and academic search complete electronic databases as well as clinicaltrials.gov (from inception up to 01 August 2022) for randomised controlled trials examining chemoimmunotherapy and targeted therapy in patients with CLL. The risk of bias and the quality of evidence was assessed using the quality in prognostic studies tool (QUIPS).A total of 10 prognostic factors were identified and evaluated in patients with CLL on anti-CD20 antibody-containing CIT. The predictive value of the following prognostic factors was confirmed and associated with poor patient outcomes; deletion 17p (HR = 3.39), Immunoglobulin heavy chain variable region gene mutation status (HR = 0.96) and β2-microglobulin (HR = 1.41).Conventional predictive factors may have retained prognostic value and could be useful in the stratification of patients who may be non-responsive to CIT.Trial registration: International Prospective Register of Systematic Reviews (PROSPERO) registry (CRD42021218997).

B Cell Subsets and Immune Checkpoint Expression in Patients with Chronic Lymphocytic Leukemia

“…The levels of B2M are independently associated with disease progression in patients with CLL [17]. In our multivariable regression model, there was no association between B2M levels and PD- S1).…”

“…The primary aim of this study was to determine the levels of immune checkpoint expression on the peripheral B cell subsets in patients with CLL and to further correlate these immune checkpoints with B2M levels, a confirmed independent prognostic marker in patients with CLL [ 17 ]. In this study, we determined the baseline expression levels of B cell subsets in patients with CLL.…”

“…To measure the plasma levels of B2M, a prognostic marker in patients with CLL [ 17 ], we made use of a beta-2 microglobulin human enzyme-linked immunosorbent assay kit (ThermoFisher Scientific, Waltham, MA, USA), according to the manufacturer’s instruction.…”

“…In our multivariable regression model, there was no association between B2M levels and PD- S1). The levels of B2M are independently associated with disease progression in patients with CLL [17]. In our multivariable regression model, there was no association between B2M levels and PD-1 on B cells (β = 0.008, SE = 0.011, p = 0.524), PD-1 on activated B cells (β = 0.008, SE = 0.011, p = 0.525), PD-1 on memory B cells (β = 0.0008, SE = 0.004, p = 0.905), CTLA-4 on B cells (β = 0.004, SE = 0.002, p = 0.426), CTLA-4 on activated B cells (β = 0.004, SE = 0.002, p = 0.419), or CTLA-4 on memory B cells (β = 0.004, SE = 0.002, p = 0.419) in patients with CLL (Supplementary Table S1).…”