Utilizing MRD To Treat Patients With Hairy Cell Leukemia

Minimal residual disease, or measurable residual disease as it’s known to some experts, usually plays an important role in the treatment of patients with leukemia, but its role in hairy cell leukemia is more controversial among experts, according to Frahad Ravandi-Kashani, MD.

At the 2019 Hairy Cell Leukemia Foundation Annual Conference, Ravandi-Kashani, professor of medicine in the department of leukemia at the University of Texas MD Anderson Cancer Center, had the chance to sit down with OncLive^®, a sister publication to Oncology Nursing News^®, and discuss the role of MRD in the treatment of patients with hairy cell leukemia and why it is not as readily accepted by professionals, and why it should be.

OncLive^®: Can you discuss the role of minimal residual disease in hairy cell leukemia?

Ravandi-Kashani: MRD, which is historically called minimal residual disease but many people refer to it as measurable residual disease, is an important marker when patients with, particularly leukemia but also other hematological malignancies, achieve what we call complete remission, which historically has been defined as complete morphological remission, meaning that the pathologists can no longer find evidence of the disease in the bone marrow by using standard microscopic assessments.

Now, we have always known that when patients achieve such a state, depending on the type of leukemia, many will relapse, which means that even when you're in morphological complete remission, you still have disease cells harboring somewhere in your body and eventually lead to relapse.

In more indolent leukemias, such as Hairy Cell leukemia, at the moment the value of MRD assessment is somewhat controversial. However, there have been studies that have shown that if you have Persistent disease at a time of remission, you are probably more likely to relapse. The original study used immunohistochemistry showing that patients who are in remission and still had evidence of disease by an immunohistochemistry in their bone marrows, they are more likely to relapse.

As we have developed more and more effective regiments, the value of this may become even more limited. So, if you have 100% of patients responding, and virtually none of them relapsing at 10 years, it's going to be difficult to use minimal residual disease. But also, there are some publications that have shown that indolent diseases such as hairy cell leukemia, you can even have a few hairy cells in your bone marrow 10, 15, or 17 years after achieving remission and still not having a full-blown relapse.

What does this mean for the current treatment of patients with hairy cell leukemia?

There are now probably better assays for detecting MRD in hairy cell leukemia such as better flow assays, as well as patient-specific immunoglobulin chain rearrangement by PCR. Now we have a marker that is positive in virtually all hairy cell patients and that is mutated BRAF.

So that could potentially be another assay. However, if we develop very effective strategies with virtually no patients relapsing, the value of MRD assessment becomes less and less.

What other treatment decisions can MRD impact?

I think in the relapse setting MRD may still be important, especially if you use strategies that are not producing 100% MRD-negative CR, because then you can think about better monitoring the patient and you may even, whether it is possible or not, want to supplement the therapy that you use for your relapse patient. So, I think there potentially could be a role for MRD assessment particularly in relapsed patients, because in the relapse setting the CR durations have tended to be shorter.

What does the future of MRD in the treatment of patients with hairy cell leukemia look like?

There are now regimens that produce high morphological and MRD-negative CRs in hairy cell leukemia, and maybe they should become the gold standard for frontline therapy.

Unfortunately, because hairy cell leukemia is an uncommon disease. It is very difficult to do large randomized trials and get this strategy FDA approved.

And personally, I struggle almost every week with patients who want to receive cladribine in and rituximab, but their insurance companies would not approve it because the current standard is cladribine alone.

However, it remains a useful extra assessment in terms of telling the patient that you’ve had an excellent response and the likelihood of relapse is almost zero.