Table 1 Summary of drug characteristics, reported infectious complications and ECIL recommendations for clinical practice
Class of agents | Agent | Impact on immune system | Infectious events | ECIL recommendations |
|---|---|---|---|---|
CD19-directed CD3 bispecific T-cell engager | Blinatumomab | B-cell aplasia; hypogammaglobulinemia; neutropenia | No clear evidence of increased infection rate | •Consideration of IgG substitution in case of serious infection |
Anti-CD30 antibody | Brentuximab vedotin | Poorly defined; impairment of memory cell generation and survival; transient neutropenia | Pneumocystis pneumonia; CMV and HBV reactivation; JC virus-associated PML | •CMV monitoring; •No routine systemic antimicrobial prophylaxis; •High alertness to PML |
Immune checkpoint inhibitors | Ipilimumab (anti-CTLA4); Nivolumab, pembrolizumab, atezolizumab and others (anti-PD-1/anti-PD-L1) | No direct immunosuppression | Frequent immune-related auto-inflammatory complications; infections due to anti-inflammatory/immunosuppressive agents | •High alertness to infections if anti-inflammatory/immunosuppressive agents are required; •Pneumocystis prophylaxis if glucocorticosteroid medication exceeds 3−4 weeks |
Bruton Tyrosine Kinase Inhibitor | Ibrutinib | Toll-like receptor-mediated recognition of infectious agents; Maturation, recruitment and function of innate immune cells, including neutrophils, monocytes and macrophages; Regulation of NLRP3 inflammasome activation | Slight increase in bacterial, fungal and viral infections, particularly in heavily pretreated patients; Cerebral aspergillosis in patients treated for lymphoma with brain involvement | •Update protective vaccinations before ibrutinib treatment; •Increased alertness to infections; •At signs of infection, diagnostics including bacterial, viral and fungal pathogens; •No routine systemic antimicrobial prophylaxis |
Phosphatidylinositol- 3-kinase inhibitor | Idelalisib | Decrease in number and function of regulatory T cells; Inhibition of NK cell and neutrophil inflammatory response; Neutropenia | Slight increase in Pneumocystis pneumonia | •Anti-Pneumocystis prophylaxis (see label); •Check CMV serostatus and consider CMV monitoring; •At signs of infection, consider immune-related adverse reaction |
Histone deacetylase inhibitors | Vorinostat, panobinostat, romidepsin | Inhibition of toll-like receptor-mediated dendritic cell and macrophage function (sensing, phagocytosis, cytokine production, adhesion) | No clear evidence of increased infection rate | •HBV screening, consideration of antiviral prophylaxis in HBsAg- or anti-HBc-positive patients |
mTOR inhibitors | Sirolimus, temsirolimus, everolimus | Inhibition of T-cell proliferation, antigen-presenting cells, B cells, neutrophil granulocytes | No clear evidence of increased infection rate | •High alertness of infections; •No routine antimicrobial prophylaxis; •At signs of pulmonary infection, consider immune-related adverse reaction |
Janus kinase inhibitor | Ruxolitinib | Inhibition of dendritic cell and CD4+ T-cell function; Reduction of regulatory T cells; NK cell inhibition | Marginally increased risk of opportunistic infections; Occasional HBV reactivation | •Careful monitoring for infections; •HBV screening, prophylactic entecavir in HBsAg- or anti-HBc-positive patients; •MTB screening in patients-at-risk |
BCL2 inhibitor | Venetoclax | Neutropenia | 15−20% grade ≥ 3 infections | •Management according to neutropenia; •Consider G-CSF; •At combination with posaconazole, venetoclax dose reduction by ≥75% |
