Elizabeth Griffiths, MD, associate professor of oncology, department of medicine, Roswell Park Comprehensive Cancer Center, discusses the prevalence of neutropenia in patients with acute myeloid leukemia and patient/clinical characteristics that can predict which patients will become neutropenic.
Elizabeth Griffiths, MD, associate professor of oncology, department of medicine, Roswell Park Comprehensive Cancer Center, discusses the prevalence of neutropenia in patients with acute myeloid leukemia (AML) and patient/clinical characteristics that can predict which patients will become neutropenic.
How prevalent is neutropenia in patients with AML, and are there any patient/clinical characteristics that can help predict which patients will become neutropenic?
Any patient who receives an intensive induction strategy is likely to have neutropenia. The neutropenia when you give an intensive induction strategy usually is relatively self-limited on the order of 2 weeks or 3 weeks. The duration of neutropenia can be more prolonged in older patients and people who have secondary leukemia who previously received chemotherapy, or in people who are frail or unfit.
Neutropenia is strongly associated with the risk of developing infections, especially invasive fungal infections. So, one of the things we do to mitigate the risks associated with neutropenia is we use a variety of prophylactic antibiotics, which are part of the big changes and the big improvements we’ve had in the standard of care for patients with AML.
When we think about alternative induction strategies; things like the hypomethylating agents alone or in combination with drugs targeting BCL2, like venetoclax. The periods of neutropenia that you get with those agents are markedly more prolonged and can be persistent for several months. This is also true for patients receiving IDH [isocitrate dehydrogenase] inhibitor therapies, where what you see is differentiation rather than cytotoxicity. And sometimes the neutropenia can last a long time.
FLT3 therapies are also associated with these periods where the patients have prolonged cytopenias but are alive. So, because we have these long periods of neutropenia, and these patients receiving alternative induction strategies or alternative therapies for relapsed and refractory disease, we have a lot of neutropenia in our patients.
These prolonged periods of neutropenia are associated with an increased risk of invasive fungal infection, and so for that reason, I think the use of prophylactic therapy for invasive fungal infection is really, really important. I think it’s also really important to recognize that the combination of venetoclax, or BCLT2 inhibitor, with effective second or third generation antifungals results in substantial changes in the bioavailability of the venetoclax, particularly.
And so, it’s important to consider dose reduction of the venetoclax in patients in whom your using a mold-active antifungal. So, that’s been described, particularly the strategy for dose reduction with posaconazole given with venetoclax has been described. I think with the other agents we have a little bit less data, but it’s certainly a substantial issue.