Managing Comorbidities in AML

James K. McCloskey II, MD:What if this 68-year-old gentleman came in to us and he had a prior history of diabetes? Maybe he’d had coronary artery bypass and was more sedentary, spent much of his day in a wheelchair or relied on his family members for a lot of his activities of daily living. This is a patient in front of me who I probably am thinking will not tolerate a stem cell transplant. It’s a patient for whom I think we would focus a lot more on the quality of life. Fortunately, there are lots of new therapies to benefit this patient population as well. But it would probably be a patient who I think many of us would argue may not experience a lot of the benefits of induction chemotherapy.

For a patient in that situation, we have a couple of other new FDA approved therapies. That would include glasdegib in combination with low-dose cytarabine, or venetoclax in combination with HMA [hypomethylating agent]. I think that we’d have a long conversation with that patient and discuss all the options. But both of those would be good options for that patient.

I think the other unique patient might be a patient who comes in to us who, for instance, maybe has an impaired performance status at the time I meet them because of complications with leukemia itself. Maybe they have a pretty severe pneumonia, an infection, and so for the time being their performance status is less than adequate for induction chemotherapy or transplant, but that with time that might be able to improve. Maybe that patient could get some rehabilitation and actually improve and go to transplant. That patient is someone who we might use 1 of these therapies as a bridge to transplant while we wait for their performance status to improve.

I think that if that patient was borderline, and at age 68 we’re deciding between intensive therapy and more gentle potentially cognitive therapy, then I think that’s a personal decision. As I mentioned, I think for any patient over the age of 65, it’s really important that we consider that patient’s own preference in terms of the toxicities that they’re willing to tolerate. But I think that would be a personal decision between us and the patients. I might err more on the side of 1 of the more gentle therapies like venetoclax and HMA, or glasdegib and low-dose cytarabine.

For other important considerations, we mentioned the patient’s preference. Some of that’s important in regard to the toxicity profile. It’s also important, too, where that patient would like to be. Because one of the important things we haven’t discussed as much is the fact that most of our patients with Vyxeos are going to be treated for a substantially longer time in the hospital. That can be something that our patients are really averse to. I think that’s another consideration we might take into account—the likelihood of hospitalization or the need for hospitalization in some settings for induction chemotherapy.

The other consideration would be that the NCCN [National Comprehensive Cancer Network] guidelines panel of experts also agreed with the importance of these improved responses in the Vyxeos arm. For patients over the age of 60 who have a secondary or treatment-related AML [acute myeloid leukemia], Vyxeos is a category 1 endorsement for induction therapy for those folks. I think this really represents our new standard of care for patients with treatment-related or secondary AML.

Transcript edited for clarity.

Case: A 68-Year-Old Man Withde novoAML

History and Physical:

• A 68-year-old man presented with significant fatigue and shortness of breath on exertion; reports low-grade fever for the past few days.
• PMH: mild hypertension, hypercholesterolemia, both medically managed; no history of malignancy

Laboratory work-up:

• WBC, 2.6 X 10⁹/L
• ANC, 1.2 X 10⁹/L
• Hb, 9.4 X 10⁹/L
• Hct, 32%
• RBC, 3.3 X 10⁹/L
• MCV, 121 fL
• PLT, 95 X 10⁹/L

Bone marrow biopsy:65% blasts

Peripheral blood smear;70% blasts

FISH;del(5q), del (20q)

Diagnosis;AML, myelodysplasia-related cytogenetic abnormalities