Table 1.
Infection risk, drug interaction and prophylactic considerations associated with the use of therapeutic agents for acute leukemia
| Chemotherapy/Biological | Use | Infection risk | Interaction | Recommendations |
|---|---|---|---|---|
| Vinca alkaloids | ALL | Regimen related | Inhibits CYP3A4 | Avoid with azole |
| Alkylating agents | ALL | Regimen related | CYP3A4/2C | Avoid with azole |
| BCR-ABL TK inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) | Ph+ ALL | Modest risk: bacterial infections, CMV, PJP, HBV reactivation | CYP3A4 inhibitor | No clear benefit from routine prophylaxis Screen for HBV infection Avoid with azole Monitor QTc |
| Anti-CD19 bispecific T-cell engager (blinatumomab) | ALL | HSV, VZV, CMV, PJP, PML, fungal per NCCN | Consider ACV and PJP prophylaxis Screen for HBV |
|
| Anti-CD22 antibody drug conjugate (inotuzumab) | ALL | Risk similar to anti-CD20 | No clear benefit from routine prophylaxis Screen for HBV infection High risk for VOD |
|
| CD19 CAR-T (tisagenlecleucel) | ALL | Increased risk for IFI, PJP, prolonged IgG hypogammaglobulinemia in long-term; distinguish infection from CRS | Acyclovir viral prophylaxis PJP prophylaxis Screen for chronic HBV Consider levofloxacin and fluconazole prophylaxis Consider anti-mold azole if high-dose steroids or prolonged neutropenia |
|
| BCL-2 inhibitor (venetoclax) | AML | Possible increased risk of fungal infections in absence of antifungal prophylaxis | CYP3A4 | Avoid with azole If azole is indicated dose reduce venetoclax (>50%) |
| IDH1/2 inhibitor (ivosidenib, enasidenib) | AML | No clear increased risk of infection; distinguish infection from differentiation syndrome | Avoid with azole Monitor QTc |
|
| Hedgehog pathway inhibitor (glasdegib) | AML | No data | CYP3A4 | Avoid with azole Monitor QTc |
| Anti-CD33 antibody drug conjugate (gemtuzumab) | AML | Prolonged myelosuppression | Monitor QTc High risk for VOD |
|
| FLT3-TK inhibitor (midostaurin and gilteritinib) | AML | No significant increased risk of fungal infection | CYP3A4 | Monitor QTc Monitor for midostaurin toxicity and use posaconazole TDM |
ACV, acyclovir; BCL-2, B-cell lymphoma 2; CAR-T, chimeric antigen receptor T cell; CMV, cytomegalovirus; CRS, cytokine release syndrome; HBV, hepatitis B virus; HSV, herpes simplex virus; IDH, isocitrate dehydrogenase; IgG, immunoglobulin G; Ph+, Philadelphia chromosome–positive; PJP, Pneumocystis jirovecii pneumonia; PML, progressive multifocal leukoencephalopathy; TK, tyrosine kinase; VOD, veno-occlusive disease; VZV, varicella zoster virus.