Discussing the Role of MRD in CLL With Talal Hilal, MD

Dr. Hilal, of the Mayo Clinic, joins Chadi Nabhan, MD, MBA, FACP, on “The HemOnc Pulse” to discuss measurable residual disease (MRD) and the debates surrounding its use for response assessment in patients with chronic lymphocytic leukemia (CLL).

“[MRD] is basically cancer cells we couldn’t measure, but now we have newer tools that can measure them—assays, flow cytometry, and next-generation sequencing,” Dr. Hilal explained. “When we talk about having ‘undetectable’ MRD, we’re talking about not being able to see cancer cells at very low sensitivities. It’s a response measure that may or may not be relevant.”

Dr. Nabhan asked Dr. Hilal for his perspective on the use of MRD.

“I’ll go back to the principle of what cancer is and what we are trying to achieve when we treat certain cancers. If you eradicate every single cell, theoretically you’re going to cure the cancer,” Dr. Hilal responded. In that context, the use of undetectable MRD status as a treatment target could increase the number of patients who are cured for good, he suggested.

Dr. Nabhan raised the question of if the current techniques and criteria for MRD are prescriptive enough.

“I’m not going to be able to say that if I achieve undetectable MRD at 10⁻⁶ in a CLL patient I cured them,” Dr. Hilal acknowledged. “But I can probably envision a situation where they are going to potentially have a better outcome than they would have five or 10 years ago if they didn’t achieve that depth of remission.”

Dr. Hilal did note that the prognostic value of MRD is still undergoing investigation in CLL, but its value as a treatment target seems relatively clear in some other diseases like acute leukemias.

In response, Dr. Nabhan asked Dr. Hilal whether he uses MRD to make treatment decisions.

“I’ve moved to using it more often in the last six to 12 months, not necessarily to drive treatment duration or treatment decisions, but mostly for prognostic purposes for patients,” Dr. Hilal answered. “Patients are becoming more aware that MRD exists and are asking about it, and sometimes having that information helps with conversations about prognosis.”

However, he noted that MRD can be less useful for other CLL treatments that are generally not associated with deep remissions. “[Bruton’s tyrosine kinase] inhibitors, for example, are not really associated with complete remissions, but mostly partial remissions.”

For time-limited therapies, Dr. Hilal said he typically wouldn’t cut treatment short if a patient achieved undetectable MRD status before finishing the planned course. Detectable MRD after therapy prompts a conversation with the patient, he added, noting that, “at this point, it’s a little bit difficult to say, let’s extend treatment, although there are more data coming out to suggest that if you do extend it and achieve MRD, you may actually have better outcomes.”