Monitoring for AML Remissions: Are We Measuring Properly?

When it comes to monitoring patients previously treated for acute myeloid leukemia (AML), determining who is in remission is still an imperfect process, according to Richard M. Stone, M.D.

Stone — who is the director of the Adult Leukemia Program at the Dana-Farber Cancer Institute and a professor of Medicine at Harvard Medical School – recently posed the question of how best to monitor minimal residual disease (MRD) in patients with AML.

“It’s a very important question to [measure] the amount of AML left after induction therapy,” he said.

MRD is typically measured by the amount of myeloblasts — commonly referred to as blasts – that remain after treatment. Blasts are immature white blood cells, and AML occurs when there are too many blasts and not enough white blood cells in a patient’s bone marrow. After treatment, physicians follow a pretty straightforward rule: If blasts levels dip below 5 percent, the patient is in remission.

“But we also know that less than 5 percent blasts in the bone marrow is still a lot of blasts,” Stone said. “So, wouldn't it be nice to have a quantitative way to say how deep the remission is? Historically, it’s been felt that if you just scratch the surface and get below the 5 percent blast level, you’re probably going to relapse. And if you get deeper, you might not.”

Health care providers currently do have techniques that can quantify the residual blast amount, Stone said. The first step in benefiting from this would be to use quantification as a prognostic marker for how these survivors may do in the future. Looking ahead, this technique may help to plan treatment strategies.

“If we could capitalize on that by either assigning different therapies for those with high levels of MRD, we might be able to improve the overall outcomes of people with AML, which is really, of course, the goal,” Stone said.

But Stone admits that, currently, he is unsure of the best method for detecting MRD. And still, some American physicians don’t monitor these levels at all.

“Unfortunately, I must confess to being uncertain about the right answer to the question of how physicians should measure MRD, and what they should do with the results,” he said. “So, at the moment, I am more or less on the side of making sure that MRD is monitored in the context of any clinical trial, so that we can learn what to do with it, possibly to design clinical trials that will determine the importance of MRD or to figure out whether using it in some way will be helpful.”

The monitoring of MRD is currently used frequently in myeloma and chronic lymphocytic leukemia, and is beginning to show progress in acute lymphoblastic leukemia. Stone is hopeful that one day, MRD will play as key a role in AML as it does with other hematologic malignancies.

“I think it’s a really great time to be a leukemia doctor taking care of these patients. In AML, we’ve had four new agents approved in 2017, so that’s a source of great excitement,” he said. “I’m really excited about new drugs, but also regarding MRD, I’m excited about the opportunity to test it, although I don’t really have all the answers yet.”