Pulmonary Coccidioidomycosis Occurring in a Patient Treated With Acalabrutinib for Chronic Lymphocytic Leukemia

TL;DR

A patient with chronic lymphocytic leukemia treated with acalabrutinib developed a rare fungal lung infection, highlighting the need for vigilance in managing immune-related risks.

Contribution

This case highlights the potential link between acalabrutinib therapy and pulmonary coccidioidomycosis in immunocompromised patients.

Findings

A patient on acalabrutinib developed pulmonary coccidioidomycosis with a Naranjo score of 4 (probable).

Combination of IVIG and antifungal therapy led to clinical improvement.

Immune defects, CLL, and prior drug exposure complicate causality assessment of fungal infections.

Abstract

Acalabrutinib is a Bruton tyrosine kinase inhibitor (BTKi) approved for use in the treatment of chronic lymphocytic leukemia (CLL). Herein, we present a patient successfully treated with reduced-dose acalabrutinib for CLL, with pre-existing hypogammaglobulinemia-type immunoglobulin G (IgG) and immunoglobulin M (IgM). Twenty-four months into therapy, he developed a right upper lobe infiltrate due to pulmonary coccidioidomycosis; the Naranjo causality assessment score was 4 (probable). The patient received monthly intravenous IG (IVIG) infusions and antifungal therapy, with significant clinical improvement. Acalabrutinib was restarted, along with close clinical monitoring. The extent to which invasive fungal infections can be attributed to acalabrutinib alone is not always straightforward due to the presence of immune defects associated with CLL, endemic zip codes, and a prior exposure to ibrutinib. Physicians should remain vigilant in assessing and managing invasive fungal infections in these patients in order to optimize patient safety and clinical outcomes.

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