Selecting Therapy for Newly Diagnosed AML

James K. McCloskey II, MD:This is a tough patient. It’s a 68-year-old gentleman, and age is just a number, but sometimes it’s an important number. At the age of 68, our patients often come to us with other comorbidities and they may not tolerate induction chemotherapy as well as their younger counterparts. One of the first things we’re really assessing is the fitness of the patient. How active are they? Are they the kind of patient who’s still working part-time, out on the golf course a few times a week, maybe still goes to the gym pretty regularly?

Or is this a patient who has other comorbidities and spends most of the day in a chair, or maybe even is wheelchair bound? This is really challenging because it’s quite variable between physicians, and we haven’t gotten good at uniformly approaching the assessment of performance status. But the first thing we consider is what does the patient look like who’s sitting in front of us?

Also, what’s important in a 68-year-old patient is what are their goals? Going through induction chemotherapy is not always easy. Even with induction chemotherapy and the improvements we’ve had in the recent years, their prognosis is still relatively poor. I think having a realistic expectation of outcome and what that patient expects in terms of their quality of life, and their personal preference is also important. But the first thing we’re trying to decide is whether we want to do induction therapy or more palliative therapy.

At our institution, we consider transplants for all of our patients up to the age of 80. That being said, as we crest 65 and 68, those transplants get more difficult, and we certainly recognize that given patients comorbidities and their age, they may have more difficulty tolerating a transplant. But multiple studies have shown that the incorporation of transplant into consolidation for patients in CR1 [first complete remission], even over the age of 60, leads to the greatest improvement in their overall survival. When a patient walks into my office, if they’re fit and healthy and interested in proceeding with induction, my goal as a leukemia physician is absolutely to get that patient into a deep CR1, and to start evaluating for typing so that we can proceed to transplant when we have a remission.

In terms of assessing a remission, I think that as time has gone by, we’ve gotten better being able to detect cancer cells. The definition of a remission continues to change. Now we talk about not only a morphologic remission but a cytogenetic remission, a molecular remission, and then minimal residual disease [MRD] testing, which can be a combination of either flow cytometry, next-generation sequencing, or even PCR [polymerase chain reaction].

What we know for sure is that patients who achieve an MRD-negative response and have no measurable residual disease have better outcomes in CR1 without a transplant. But even more importantly, these are patients who have better outcomes with a transplant. For a patient who we achieve an MRD-negative remission in, we’re even more optimistic as they proceed to transplant that they’ll do well after the transplant as well.

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