Therapy regimens and infection risk differ in the setting of chronic leukemia. Cytotoxic chemotherapy is standard in the first-line setting for chronic lymphocytic leukemia (CLL), and CLL is often associated with hypogammoglobulinemia that can lead to frequent infections. In contrast, chronic myeloid leukemia is generally treated with tyrosine kinase inhibitors that target the BCR-ABL fusion protein, and classical myeloproliferative neoplasms (MPN) are usually treated with hydroxyurea. If the dose of hydroxyurea is titrated to avoid neutropenia, the risk for infection with this agent is minimal.
For lymphomas, multiagent chemotherapy with or without the addition of monoclonal antibodies remains the backbone of treatment. Both high-grade non-Hodgkin lymphoma and Hodgkin lymphoma can be treated with regimens such as cyclophosphamide, doxorubicin, vincristine or etoposide, and prednisone with rituximab (R-CHOP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Estimated incidence of febrile neutropenia for these treatment regimens is 15% to 22%.
Patients with plasma cell myeloma may have a preexisting risk of infection due to producing antibodies with restricted repertoires. A large population-based study spanning 1988 to 2007 reported that within the first 60 days after diagnosis, 10% of all patient deaths were related to infection. However, treatment of myeloma has significantly evolved over the past 10 years. Another study assessing the effect of prophylactic antibiotics on infection rate in newly diagnosed patients with myeloma reported a decrease in incidence of febrile episodes or death (19% vs 27%; P =.002) at 12 weeks as well as a reduced rate of gram-negative infections. Nonetheless, though limiting the duration of infectious prophylaxis could be considered in this setting, it is not currently the standard of care.
Managing Drug Risks
In addition to chemotherapy and steroids, an increasing armamentarium of novel agents is being used to treat these diseases, including signaling and small molecule inhibitors, monoclonal antibodies, immunomodulators, and immunotherapies. Although cytotoxic chemotherapy is associated with predictable infectious risks, the long-term safety data and specific infectious risks of newer agents are not as clear and require further study.
“Sometimes we also expose patients to immunosuppressive medications to treat side effects of cancer therapies, such as steroids for treatment of immune mediated adverse events from checkpoint inhibitors,” said Dr He.
The authors highlighted the key strategies for identifying and managing infectious risk with specific drug classes and agents. They noted that purine analogues, the monoclonal antibody alemtuzumab, and multiagent cytotoxic chemotherapy used to treat patients with acute leukemias confer the highest risk for infection. Because reactivation is common, they recommended assessing patients for hepatitis B serostatus when administering BCR-ABL tyrosine kinase inhibitors, the Janus kinase inhibitor ruxolitinib, and rituximab. When administering the oral phosphatidylinositol 3-kinase inhibitor idelalisib, purine analogues, or the steroid prednisone, the authors suggested pneumocystis prophylaxis should be given to all patients.
Cytokine release syndrome is a common side effect of chimeric antigen receptor T-cell (CAR-T) therapy that mimics infection. “CAR-T infusion [can lead to] short-term immunosuppression related to lymphodepleting chemotherapy and inflammation from cytokine release syndrome causing bone marrow suppression, and potentially long-term hypogammaglobulinemia from B-cell aplasia requiring regular intravenous immunoglobulin repletion,” said Dr He. “For immunotherapies that are given without lymphodepleting chemotherapy, immunosuppression will be directly related to crossreactivity of the antigen target with other cell types, prior chemotherapy and bone marrow reserve, and cytokine release syndrome.”
Because of the heterogeneity of patients’ performance status, comorbidities, and disease status at time of treatment, the authors recommended treating this review as a guideline to contextualize infectious risk in patients with hematologic malignancies. “The underlying disease and prior cytotoxic treatments have paramount importance in judging the overall infectious risk with each agent,” they wrote.
1. Atkins S, He F. Chemotherapy and beyond: infections in the era of old and new treatments for hematologic malignancies [published online March 30, 2019]. Infect Dis Clin N Am. doi:10.1016/j.jdc.2019.01.001