Table 2. Infection risk associated with... | American Society of Hematology

Table 2. Infection risk associated with therapy-related immunosuppression

	Therapy-related immunosuppression	Infection risk	Considerations
Chronic lymphocytic leukemia	CD52 target (eg, alemtuzumab)	Fungal, HSV, VZV, CMV, listeria, BK, PML, and TB	PJP prophylaxis if CD4 < 200 ACV prophylaxis Monitor for CMV reactivation Screen and treat for HBV and latent TB
	Purine-analog (eg, fludarabine and cladribine)	Fungal, PJP, HSV, and VZV	During neutropenia consider bacterial, fungal, and ACV prophylaxis Consider PJP prophylaxis^*
	Bruton-kinase inhibitors (eg, Ibrutinib and alcalabrutinib)	Fungal, PJP, and PML	Consider PJP and ACV prophylaxis Monitor for fungal infection with concomitant risk factors (eg, prolonged steroids and neutropenia), consider mold-active prophylaxis Triazoles increase drug concentrations
	Phosphatidylinositol-3 kinase (PIK3) inhibitors (eg, copanlisib and idelasilib)	Fungal, PJP, CMV, and PML	PJP prophylaxis Monitor for CMV reactivation Monitor for drug-induced pneumonitis, colitis, rash, and hepatitis
	CD20 target (eg, rituximab, ofatumumab, and obinatuzumab)	HBV, HCV, VZV, PML, neutropenia, and Low IgG	Consider ACV prophylaxis^* Screen and treat for latent HBV PJP prophylaxis if used with prednisone ≥20 mg or equivalent × 4 weeks)
Multiple myeloma	Ubiquitin-proteasome pathway inhibitor (eg, bortezomib, ixazomib, and carfilzomib)	Pneumonia, influenza, and VZV	Consider ACV prophylaxis Screen for previous VZV infection and vaccinate if seronegative^† Consider recombinant, adjuvanted zoster vaccine
	Immunomodulatory drugs (eg, thalidomide, lenalidomide, and pomalidomide)	No clear increased infection risk from drug	Consider ACV and PJP prophylaxis in combination with other chemotherapies
	CD38 target (eg, daratumumab)	Neutropenia, VZV, PJP, and low IgG	ACV prophylaxis Consider PJP prophylaxis Consider screening and treating for HBV (if on concomitant steroid therapy)
	SLAMF7, CD319 target (eg, elotuzumab)	VZV and PJP	ACV prophylaxis Consider PJP prophylaxis
Hairy cell leukemia	Purine-analog (eg, fludarabine and cladribine)	Fungal, PJP, HSV, and VZV	During neutropenia consider bacterial, fungal, and ACV prophylaxis Consider PJP prophylaxis
	CD20 target (eg, rituximab, ofatumumab, and obinatuzumab)	HSV, VZV, and PJP	ACV prophylaxis Screen and treat for latent HBV PJP prophylaxis if used with prednisone ≥20 mg or equivalent × 4 weeks
	Moxetumomab pasudotox	HSV, VZV, and PJP	PJP prophylaxis if used with prednisone ≥10 mg or equivalent × 4 weeks) or CD4 count <200 ACV prophylaxis if used with chronic steroids or with lymphopenia
	Vemurafenib	No clear increased infection risk from drug	Triazoles increase drug levels May develop drug fever and skin rash
Hodgkin lymphoma	CD30 target (eg, brentuximab)	HSV, CMV, PJP, PML, and neutropenia	Monitor for CMV reactivation Consider PJP and HSV prophylaxis^* Screen and treat latent HBV if given as part of combination regimen (eg, with prednisone)
	mTOR inhibitors (eg, everolimus and sirolimus)	VZV, HBV, HCV, PJP, PML, and TB	Screen and treat HBV and latent TB Consider PCP prophylaxis Drug-related pneumonitis Triazoles increase drug levels May slow wound healing
	Checkpoint inhibitors (eg, nivolumab and pembrolizumab)	No clear increased infection risk from drug, but the drug leads to immune upregulation, which can necessitate steroids	Immune-related toxicity: colitis, hepatitis, pneumonitis, and rash Screen for HBV and latent TB if used with steroids PJP prophylaxis if used with prednisone >20 mg or equivalent × 4 weeks Some concern for giving vaccines (eg, influenza) with checkpoint inhibitors given concerns for increased adverse effects or decreased efficacy of immune therapy
Non-Hodgkin lymphoma	CD52 target (eg, alemtuzumab)	Fungal, HSV, VZV, CMV, listeria, BK, PML, and TB	PJP prophylaxis if CD4 < 200 ACV prophylaxis Monitor for CMV reactivation Screen and treat for HBV and latent TB
	CD19 directed (eg, axicabtagene ciloleucel and tisagenlecleucel)	Bacterial, fungal, HSV, HBV, PJP, and low IgG	Monitor for cytokine release syndrome, which may appear like sepsis ACV prophylaxis Screen and treat latent HBV PJP prophylaxis if used with prednisone ≥20 mg or equivalent × 4 weeks During period of neutropenia consider fluoroquinolone and fluconazole prophylaxis. Consider mold prophylaxis if long duration of high-dose steroids, depending on clinical context
	CD20 target (eg, rituximab, ofatumumab, and obinatuzumab)	HBV, HCV, VZV, PML, neutropenia, and Low IgG	Consider ACV prophylaxis^* Screen and treat for latent HBV PJP prophylaxis if used with therapy that increases risk of PJP (eg, prednisone >20 mg × 4 weeks)
	Bruton-kinase inhibitors (eg, Ibrutinib and alcalabrutinib)	Fungal, PJP, and PML	Consider PJP and ACV prophylaxis Monitor for fungal infection with concomitant risk factors (eg, prolonged steroids and neutropenia), consider mold-active prophylaxis Triazoles increase drug concentrations
	BCL-2 inhibitor (eg, venetoclax)	VZV and PJP	Consider ACV and PJP prophylaxis
	Ubiquitin-proteasome pathway inhibitors (eg, bortezomib, ixazomib and carfilzomib)	Pneumonia, influenza, and VZV	Consider ACV prophylaxis Screen for previous VZV infection and vaccinate if seronegative Consider recombinant, adjuvanted zoster vaccine
	mTOR inhibitors (eg, everolimus and sirolimus)	VZV, HBV, HCV, PJP, PML, and TB	Screen and treat HBV and latent TB Consider PCP prophylaxis Drug-related pneumonitis Triazoles increase drug levels May slow wound healing
	PI3K inhibitors (eg, copanlisib and idelasilib)	Fungal, PJP, PML, and CMV	PJP prophylaxis Consider monitoring for CMV reactivation Monitor for drug-induced pneumonitis, colitis, rash, and hepatitis
	Checkpoint inhibitors (eg, nivolumab and pembrolizumab)	No clear increased infection risk from drug, but the drug leads to immune upregulation, which can necessitate steroids	Immune-related toxicity: colitis, hepatitis, pneumonitis, and rash Screen for HBV and latent TB if used with steroids PJP prophylaxis if used with prednisone >20 mg or equivalent × 4 weeks Some concern for giving vaccines (eg, influenza) with checkpoint inhibitors given concerns for increased adverse effects or decreased efficacy of immune therapy
ACV, acyclovir; BK, BK virus; CMV, cytomegalovirus; HBV, hepatitis B virus; IgG, immunoglobulin G; PML, progressive multifocal leukoencephalopathy; TB, tuberculosis.^*Paucity of prospective data to inform institutional practices.^†Per NCCN guidelines.

	Therapy-related immunosuppression	Infection risk	Considerations
Chronic lymphocytic leukemia	CD52 target (eg, alemtuzumab)	Fungal, HSV, VZV, CMV, listeria, BK, PML, and TB	PJP prophylaxis if CD4 < 200 ACV prophylaxis Monitor for CMV reactivation Screen and treat for HBV and latent TB
	Purine-analog (eg, fludarabine and cladribine)	Fungal, PJP, HSV, and VZV	During neutropenia consider bacterial, fungal, and ACV prophylaxis Consider PJP prophylaxis^*
	Bruton-kinase inhibitors (eg, Ibrutinib and alcalabrutinib)	Fungal, PJP, and PML	Consider PJP and ACV prophylaxis Monitor for fungal infection with concomitant risk factors (eg, prolonged steroids and neutropenia), consider mold-active prophylaxis Triazoles increase drug concentrations
	Phosphatidylinositol-3 kinase (PIK3) inhibitors (eg, copanlisib and idelasilib)	Fungal, PJP, CMV, and PML	PJP prophylaxis Monitor for CMV reactivation Monitor for drug-induced pneumonitis, colitis, rash, and hepatitis
	CD20 target (eg, rituximab, ofatumumab, and obinatuzumab)	HBV, HCV, VZV, PML, neutropenia, and Low IgG	Consider ACV prophylaxis^* Screen and treat for latent HBV PJP prophylaxis if used with prednisone ≥20 mg or equivalent × 4 weeks)
Multiple myeloma	Ubiquitin-proteasome pathway inhibitor (eg, bortezomib, ixazomib, and carfilzomib)	Pneumonia, influenza, and VZV	Consider ACV prophylaxis Screen for previous VZV infection and vaccinate if seronegative^† Consider recombinant, adjuvanted zoster vaccine
	Immunomodulatory drugs (eg, thalidomide, lenalidomide, and pomalidomide)	No clear increased infection risk from drug	Consider ACV and PJP prophylaxis in combination with other chemotherapies
	CD38 target (eg, daratumumab)	Neutropenia, VZV, PJP, and low IgG	ACV prophylaxis Consider PJP prophylaxis Consider screening and treating for HBV (if on concomitant steroid therapy)
	SLAMF7, CD319 target (eg, elotuzumab)	VZV and PJP	ACV prophylaxis Consider PJP prophylaxis
Hairy cell leukemia	Purine-analog (eg, fludarabine and cladribine)	Fungal, PJP, HSV, and VZV	During neutropenia consider bacterial, fungal, and ACV prophylaxis Consider PJP prophylaxis
	CD20 target (eg, rituximab, ofatumumab, and obinatuzumab)	HSV, VZV, and PJP	ACV prophylaxis Screen and treat for latent HBV PJP prophylaxis if used with prednisone ≥20 mg or equivalent × 4 weeks
	Moxetumomab pasudotox	HSV, VZV, and PJP	PJP prophylaxis if used with prednisone ≥10 mg or equivalent × 4 weeks) or CD4 count <200 ACV prophylaxis if used with chronic steroids or with lymphopenia
	Vemurafenib	No clear increased infection risk from drug	Triazoles increase drug levels May develop drug fever and skin rash
Hodgkin lymphoma	CD30 target (eg, brentuximab)	HSV, CMV, PJP, PML, and neutropenia	Monitor for CMV reactivation Consider PJP and HSV prophylaxis^* Screen and treat latent HBV if given as part of combination regimen (eg, with prednisone)
	mTOR inhibitors (eg, everolimus and sirolimus)	VZV, HBV, HCV, PJP, PML, and TB	Screen and treat HBV and latent TB Consider PCP prophylaxis Drug-related pneumonitis Triazoles increase drug levels May slow wound healing
	Checkpoint inhibitors (eg, nivolumab and pembrolizumab)	No clear increased infection risk from drug, but the drug leads to immune upregulation, which can necessitate steroids	Immune-related toxicity: colitis, hepatitis, pneumonitis, and rash Screen for HBV and latent TB if used with steroids PJP prophylaxis if used with prednisone >20 mg or equivalent × 4 weeks Some concern for giving vaccines (eg, influenza) with checkpoint inhibitors given concerns for increased adverse effects or decreased efficacy of immune therapy
Non-Hodgkin lymphoma	CD52 target (eg, alemtuzumab)	Fungal, HSV, VZV, CMV, listeria, BK, PML, and TB	PJP prophylaxis if CD4 < 200 ACV prophylaxis Monitor for CMV reactivation Screen and treat for HBV and latent TB
	CD19 directed (eg, axicabtagene ciloleucel and tisagenlecleucel)	Bacterial, fungal, HSV, HBV, PJP, and low IgG	Monitor for cytokine release syndrome, which may appear like sepsis ACV prophylaxis Screen and treat latent HBV PJP prophylaxis if used with prednisone ≥20 mg or equivalent × 4 weeks During period of neutropenia consider fluoroquinolone and fluconazole prophylaxis. Consider mold prophylaxis if long duration of high-dose steroids, depending on clinical context
	CD20 target (eg, rituximab, ofatumumab, and obinatuzumab)	HBV, HCV, VZV, PML, neutropenia, and Low IgG	Consider ACV prophylaxis^* Screen and treat for latent HBV PJP prophylaxis if used with therapy that increases risk of PJP (eg, prednisone >20 mg × 4 weeks)
	Bruton-kinase inhibitors (eg, Ibrutinib and alcalabrutinib)	Fungal, PJP, and PML	Consider PJP and ACV prophylaxis Monitor for fungal infection with concomitant risk factors (eg, prolonged steroids and neutropenia), consider mold-active prophylaxis Triazoles increase drug concentrations
	BCL-2 inhibitor (eg, venetoclax)	VZV and PJP	Consider ACV and PJP prophylaxis
	Ubiquitin-proteasome pathway inhibitors (eg, bortezomib, ixazomib and carfilzomib)	Pneumonia, influenza, and VZV	Consider ACV prophylaxis Screen for previous VZV infection and vaccinate if seronegative Consider recombinant, adjuvanted zoster vaccine
	mTOR inhibitors (eg, everolimus and sirolimus)	VZV, HBV, HCV, PJP, PML, and TB	Screen and treat HBV and latent TB Consider PCP prophylaxis Drug-related pneumonitis Triazoles increase drug levels May slow wound healing
	PI3K inhibitors (eg, copanlisib and idelasilib)	Fungal, PJP, PML, and CMV	PJP prophylaxis Consider monitoring for CMV reactivation Monitor for drug-induced pneumonitis, colitis, rash, and hepatitis
	Checkpoint inhibitors (eg, nivolumab and pembrolizumab)	No clear increased infection risk from drug, but the drug leads to immune upregulation, which can necessitate steroids	Immune-related toxicity: colitis, hepatitis, pneumonitis, and rash Screen for HBV and latent TB if used with steroids PJP prophylaxis if used with prednisone >20 mg or equivalent × 4 weeks Some concern for giving vaccines (eg, influenza) with checkpoint inhibitors given concerns for increased adverse effects or decreased efficacy of immune therapy
ACV, acyclovir; BK, BK virus; CMV, cytomegalovirus; HBV, hepatitis B virus; IgG, immunoglobulin G; PML, progressive multifocal leukoencephalopathy; TB, tuberculosis.^*Paucity of prospective data to inform institutional practices.^†Per NCCN guidelines.

ACV, acyclovir; CMV, cytomegalovirus; HBV, hepatitis B virus; HSV, herpes simplex virus; IgG, immunoglobulin G; PJP, Pneumocystis jirovecii pneumonia; PML, progressive multifocal leukoencephalopathy; TB, tuberculosis; VZV, varicella-zoster virus.

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