Documented Infections and Mortality in Patients Receiving Bruton Tyrosine Kinase Inhibitors: A Single-Center Retrospective Cohort of B-Cell Malignancies and Chronic Graft-Versus-Host Disease

Background/Objectives: Infection burden during Bruton tyrosine kinase inhibitor (BTKi) treatment is difficult to interpret when infection onset, treatment initiation, and discontinuation are incompletely documented. We described the timing, microbiology, and mortality of documented infections and explored the association between peri-initiation albumin and documented infection. Methods: This retrospective single-center cohort included 76 patients treated with ibrutinib or acalabrutinib for B-cell malignancies or chronic graft-versus-host disease (cGVHD). The first documented on-treatment infection was analyzed using Aalen–Johansen cumulative incidence, with death or permanent treatment discontinuation as competing events. Sensitivity analyses included a day-30 landmark analysis, a total-burden analysis that also counted infections after discontinuation, and indication-specific estimates. Albumin associations were assessed through day 90, with Benjamini–Hochberg correction across seven exploratory comparisons. Results: Fifty-eight patients had B-cell malignancies and 18 had cGVHD; median follow-up by reverse Kaplan–Meier was 244 days. A qualifying infection occurred in 27/76 patients (35.5%); 17/27 were recorded within 30 days, of which one was suggestive of pre-existing infection and 16 were indeterminate. The cumulative incidence at day 180 was 30.5% (95% CI 19.9–41.5%) on treatment and 38.1% (95% CI 26.2–50.4%) when post-discontinuation infections were included. Among 49 patients still eligible at day 30, the conditional incidence by original day 180 was 11.2% (95% CI 2.4–21.3%). Respiratory and urinary foci accounted for 13/27 and 9/27 infections, respectively. Twenty-nine patients (38.2%) died; 17/29 deaths were recorded as infection-related. Median albumin was lower in patients with infection by day 90 (3.05 versus 3.80 g/dL; nominal p = 0.009), but this exploratory difference did not meet the multiplicity-adjusted threshold (q = 0.065) and attenuated when first-week infections were excluded. Conclusions: Documented infections and infection-related deaths were frequent in this heterogeneous cohort, but uncertain onset limits the interpretation of the early cluster. The albumin finding is hypothesis-generating and does not establish prediction or causation.