Yehuda Deutsch, MD, and Amanda Brahim, PharmD, BCOP, BCPS, BCACP, review the risks and precautions taken with the available treatments of acute myeloid leukemia (AML).
Katie Culos, PharmD, BCOP: Yehuda, as the treating physician, what are some important safety concerns or things for you to consider when you’re looking at different treatment options for your AML [acute myeloid leukemia] patients?
Yehuda Deutsch, MD: We all have to realize that patients with AML typically are quite sick. So, there always can be concerns about low blood counts, cytopenias, transfusion requirements, and risk of infections. We have to take that into account when we’re looking at the toxicities of these medications. Number 1 is cytopenias. Many of these therapies can cause prolonged cytopenias, especially those like the induction chemotherapies. CPX351 also causes probably even a longer duration of cytopenias than the standard induction 7 + 3. Regarding the other types of toxicities, some of them are more unique.
We all know that with treatment for APL [acute promyelocytic leukemia] there’s risk of differentiation syndrome, and we now see that some of the newer targeted therapies, especially the IDH inhibitors, but even the FLT3 inhibitors, can cause differentiation syndrome. We need those that are prescribing and taking care of these patients to watch out and monitor their patients closely for the risk of differentiation syndrome. Typically, these patients can have fevers, they can have volume overload, shortness of breath, and sometimes increasing white blood cell count.
The other, more common types of adverse effects, especially from cytotoxic therapies, are things like tumor lysis syndrome, which most people are accustomed to monitoring for…in acute myeloid leukemia. We monitor labs very closely. For example, venetoclax, typically is supposed to have a high risk of tumor lysis syndrome and some other hematologic malignancies. We don’t see that very often in AML. However, we do have to be really cautious and monitor for tumor lysis syndrome and also prophylax them with allopurinol.
Amanda Brahim, PharmD, BCOP, BCPS, BCACP: I think it’s important to note, too, that since some of these are newer agents, and we’re treating patients on an outpatient basis as well, counseling patients and telling them what to expect and what side effects to look out for is really important.
Yehuda Deutsch, MD: When prescribing these medications, when we’re reviewing these medications with patients, especially in the outpatient setting, we’re discussing them with the physicians and with nurse practitioners, and the pharmacist as well. There are certain dedicated outpatient pharmacists in the clinic, as well as in specialty pharmacy, that typically either see the patients in clinic in person or talk with them over the telephone, going over these specific adverse effects.
Katie Culos, PharmD, BCOP: We mentioned that one of the big risks in this patient population, due to having prolonged cytopenias, will be risk for infection. Amanda, knowing there is a lot of oral agents on the market, can you comment on how you guys have managed your drug interactions with different agents and your choice? Specifically, we definitely think of azole antifungals right away when anyone says drug interaction.
Amanda Brahim, PharmD, BCOP, BCPS, BCACP: Yes, at our institution, we generally like to prophylax against fungal infections with azoles. Our drug of choice generally is posaconazole. However, specifically, venetoclax comes to mind, where there is a significant drug interaction. What we've done is we try to use isavuconazole whenever possible, but sometimes you struggle with getting approval on the outpatient setting for that. We do have pharmacists who are monitoring patients and dose adjusting ahead of time to try and manage this interaction. Now, we've dropped down to a dose of 100 generally, when we have a strong CYP3A4 inhibitor, but it's nice to know that even if the effective dose were to be higher, we do have safety data all the way up until 1200 milligrams for venetoclax. We generally are able to manage, and patients have been able to manage those adverse effects.