CLL-105 Cumulative Incidence of Grade 3 or Higher Infections in Patients With CLL/SLL Treated With BTKi-Based Regimens

Context: Bruton tyrosine kinase inhibitors (BTKi) have shifted the treatment approach for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Objective: To calculate the incidence of grade 3 or higher infections among patients with CLL/SLL who are treated with a BTKi-based regimen. Methods/Design: We searched the PubMed and EMBASE databases for randomized controlled trials (RCTs) and performed a random-effects meta-analysis to estimate the cumulative incidence of infections among patients receiving BTKi-based treatment. We followed the PRISMA statement for systematic reviews and meta-analyses and performed the analysis using the DerSimonian and Laird approach. For this analysis we focused on infections grade 3 or higher. Results: Ten studies fulfilled our criteria and provided data on 2,672 patients with a follow-up period from 9.1 to 40.9 months. These studies were published between 2014 and 2022 and included 15 BTKi-based regimens. A total of 558 patients with infections provided a pooled cumulative incidence of 19.86% (95% CI: 16.03-23.98%). The most common infections reported were pneumonia (2.2–10.5%), upper respiratory tract infections (0.4-2.9%), and urinary tract infections (0-4%). In 8 studies BTKi was used as monotherapy and 352 patients had infections with a pooled cumulative incidence of 20.7% (95% CI: 16.48-25.26%). Five studies provided data on BTKi agents as part of a combination treatment and 206 patients developed infections with a pooled incidence of 18.54% (95% CI: 11.37-26.96%). Interestingly, in subgroup analysis, we found a statistically significant subgroup effect based on the treatment setting (treatment naïve vs. relapsed/refractory). Specifically, treatment naïve patients had a pooled incidence of 16.22% (95% CI: 12.5-20.31%), compared to 25.84% (95% CI: 20.65-31.39%) among those with relapsed or refractory disease. Conclusions: Almost 1 out of 5 patients (19.86%) receiving a BTKi agent for the management of CLL/SLL will develop a high-grade infection. Patients with relapsed/refractory disease are more likely to develop an infection compared to those that are treatment naïve. Continued surveillance and post-market trials are needed to study these infectious complications, identify high-risk patients and those at risk for multiple severe infections, and develop effective prophylactic strategies.