# Efficacy and safety analysis of the use of ibrutinib associated with rituximab for the first-line treatment of patients with chronic lymphocytic leukaemia

## TL;DR

This study compares the effectiveness and safety of two treatments for chronic lymphocytic leukaemia, finding that one combination improves survival without significant safety issues.

## Contribution

A systematic review and meta-analysis comparing ibrutinib plus rituximab to the standard FCR regimen for first-line CLL treatment.

## Key findings

- The IR regimen significantly improved progression-free survival compared to FCR.
- Overall survival did not differ significantly between the two regimens.
- Safety profiles were comparable, though evidence certainty was low for some outcomes.

## Abstract

Chronic lymphocytic leukaemia, a common blood cancer in adults, particularly affects the elderly and is marked by the accumulation of B lymphocytes. While therapeutic options have expanded, the fludarabine, cyclophosphamide, and rituximab (FCR) regimen remains the standard first-line treatment for fit patients in the Brazilian public health system.

This systematic review aimed to assess the efficacy and safety of ibrutinib plus rituximab (IR) as a first-line therapy for chronic lymphocytic leukaemia.

Following PRISMA guidelines and registered in PROSPERO (CRD42023494868), searches were conducted in multiple databases in December 2023 to identify relevant randomized controlled trials comparing the IR and FCR regimens. Eligible studies reported at least one of the following outcomes: progression-free survival, overall survival, severe adverse events, or quality of life.

Two double-blind randomized controlled trials (FLAIR and E1912) totalling 1300 patients met inclusion criteria. Meta-analysis showed that the IR regimen significantly improved progression-free survival compared to the FCR regimen (Hazard ratio: 0.41; 95% CI: 0.31–0.53) with moderate certainty of evidence. However, overall survival did not differ substantially (Hazard ratio: 0.71; 95% CI: 0.33–1.49), and the certainty of the evidence was very low. Quality of life data were unavailable. Due to variations in follow-up, results for severe adverse events were not pooled and the individual studies reported results with low certainty of evidence. The global risk of bias was rated as there was some concern due to the lack of concealed allocation in all outcomes.

The IR regimen demonstrated superior progression-free survival and comparable safety to the FCR regimen suggesting it is an effective and safe option for first-line treatment of chronic lymphocytic leukaemia.