Pneumocystis jirovecii Pneumonia in Haematology Patients Treated with Bispecific Antibodies, CAR-T Cell Therapy and Targeted Small Molecules

Purpose of Review With the expansion of new targeted and immune-based therapies, there is increased uncertainty regarding Pneumocystis jirovecii pneumonia (PJP) risk and use of prophylaxis. Bispecific antibodies, chimeric antigen receptor (CAR)-T cell therapy, B-cell lymphoma-2 (BCL-2) inhibitors and Bruton tyrosine kinase (BTK) inhibitors cause distinct immune deficits. Determining PJP risk in patients treated with these agents is important to inform evidence-based prophylaxis strategies. Recent Findings PJP risk is infrequently and incompletely described in early clinical trials of novel therapies for haematological malignancies. Although observational studies and case series highlight the need for ongoing surveillance and consistent reporting of prophylaxis use and PJP events, it is essential to define treatment-associated risk and inform the role of routine PJP prophylaxis in clinical practice. Current guidelines are based on limited evidence and inconsistencies in guideline recommendations further contribute to variability in prophylaxis practices. Summary Despite the rapid increase in clinical exposures to bispecific antibodies, CAR-T cell therapies, BCL-2 inhibitors and BTK inhibitors, the magnitude and timing of PJP risk remains uncertain. PJP risk is high in recipients of CAR-T cell therapy, for whom routine prophylaxis is recommended; moderate and frequently reported in recipients of bispecific antibodies; and low to variable in recipients of BTK and BCL-2 inhibitors, respectively, for whom prophylaxis is generally reserved for those with additional risk factors. Prospective studies with standardised PJP surveillance and prophylaxis reporting are required to define high-risk populations and periods of vulnerability, enabling risk-stratification prophylaxis recommendations that balance PJP prevention against toxicity and treatment burden.