Clinical bottom line
Patients with hematologic malignancies receiving immune checkpoint inhibitor (ICI) therapy represent a growing population at risk for infectious complications due to underlying immunosuppression and immune modulation by ICIs. Current evidence suggests that while ICIs do not inherently increase infection rates compared to other cancer therapies, vigilance is warranted for immune-related adverse events (irAEs) requiring immunosuppressive treatment, which substantially elevates infection risk. Prophylactic strategies and close monitoring tailored to the patient’s hematologic disease, ICI regimen, and irAE profile are essential. Early recognition and management of infections, including opportunistic pathogens, remain critical to optimize outcomes in this complex clinical scenario.
What the evidence shows
Immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies, have transformed treatment paradigms for various hematologic malignancies such as Hodgkin lymphoma and certain non-Hodgkin lymphomas. Unlike traditional cytotoxic chemotherapy, ICIs primarily modulate immune checkpoints to enhance antitumor immunity rather than cause direct myelosuppression. Consequently, baseline infection risk attributable solely to ICIs appears lower than with conventional chemotherapy (Delyon et al., 2021). However, immune-related adverse events (irAEs) affecting organs like the skin, lungs, and gastrointestinal tract occur in up to 20-30% of patients and often necessitate corticosteroids or other immunosuppressants, which significantly increase susceptibility to bacterial, viral, and fungal infections (Puzanov et al., 2017; Wang et al., 2018).
A systematic review by Wang et al. (2018) encompassing multiple cancer types, including hematologic malignancies, found that infection incidence during ICI therapy ranged from 5% to 20%, with opportunistic infections such as Pneumocystis jirovecii pneumonia and invasive fungal infections reported mainly in patients receiving immunosuppressive treatment for irAEs. Another cohort study focusing on hematologic malignancy patients treated with ICIs reported that infection-related hospitalization was predominantly associated with irAE management rather than the ICI itself (Delyon et al., 2021).
Regarding prophylaxis, guidelines remain extrapolated from solid tumor oncology and hematopoietic stem cell transplant literature. Prophylactic antimicrobials may be considered for patients receiving prolonged high-dose corticosteroids (>20 mg prednisone equivalent daily for >4 weeks) or additional immunosuppressants such as infliximab (Puzanov et al., 2017). Vaccination strategies, including inactivated influenza and pneumococcal vaccines, are recommended before or during ICI therapy, although data specific to hematologic malignancies are limited (Hwang et al., 2020).
Caveats and uncertainty
Most data derive from retrospective cohorts or studies including mixed cancer populations, limiting the specificity of infection risk estimates for hematologic malignancies. The heterogeneity of hematologic diseases, prior therapies, and ICI regimens complicates risk stratification. Furthermore, the evolving landscape of combination therapies (e.g., ICIs with targeted agents or chemotherapy) may alter infection risk profiles.
The timing and severity of irAEs vary widely, and the optimal thresholds for initiating prophylaxis remain undefined. Additionally, the impact of ICIs on latent infections such as tuberculosis or viral hepatitis in hematologic malignancy patients is not well characterized, warranting cautious screening and monitoring. Emerging data on the microbiome’s role in modulating ICI efficacy and toxicity add complexity but require further validation (Derosa et al., 2022).
How this may change practice
Clinicians managing infections in hematologic malignancy patients receiving ICIs should maintain heightened awareness of irAE-related immunosuppression as a key driver of infection risk. Early multidisciplinary collaboration with oncology and infectious disease specialists is advisable for individualized risk assessment and prophylaxis decisions.
Routine infection screening and vaccination should be integrated into care pathways before and during ICI therapy. Prompt evaluation and empiric treatment of suspected infections are critical, especially in patients on corticosteroids or other immunosuppressants for irAEs.
Future practice may incorporate biomarker-guided approaches to predict irAE risk and tailor immunosuppressive therapy, potentially mitigating infection complications. Prospective studies are needed to refine prophylactic strategies and define optimal monitoring protocols in this population.