Resistant Disease: When Patients with Hairy Cell Leukemia Don’t Respond to Treatment

Confirming the correct diagnosis of hairy cell leukemia: For those patients with hairy cell leukemia who don’t respond to front-line drugs (cladribine or pentostatin), it is important to establish that the correct diagnosis was made. This normally requires flow cytometry of the blood (laser-based technology that analyzes characteristics of cells) and preferably of the bone marrow. There are specific markers that are characteristically found on the leukemic cells from patients with classic hairy cell leukemia. The markers on the leukemic cells may provide a clue that the non-responding patient has a variant of hairy cell leukemia. These patients can undergo analysis of the BRAF expression to further delineate whether the patient has either the classic form of the disease or a variant. Confirmation of the underlying diagnosis enables decisions to be made about treatment.

Patients with the atypical variant of hairy cell leukemia do not respond as well to the standard agents and may have a short-lived, partial response. The variant form of hairy cell leukemia is now recognized as a separate clinical entity from the classic disease, and is recognized as being less responsive to therapy with standard treatment. Some patients with the variant form of hairy cell leukemia have responded to the combination of cladribine and rituximab. In addition, moxetumomab pasudotox was more recently approved by the FDA for the treatment of adult patients with hairy cell leukemia and hairy cell leukemia variant who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog.

Confirming why the patient is not responding: For patients with hairy cell leukemia who do not seem to respond to treatment (often called “assumed failure to respond”), it is important to accurately confirm the response before the patient undergoes re-treatment. For example, in some cases, patients have low blood counts for months after treatment, due to the toxicity of either cladribine or pentostatin. Given time, the patients in these cases may achieve a remission. Furthermore, some patients may develop “resistant” disease after having had multiple relapses with progressively shorter remission durations over time. It is important to understand why the patient is not responding to treatment (i.e., either incorrect diagnosis, delayed recovery from treatment-induced toxicity, or eventual evolution of resistant clones of leukemic cells following extensive prior treatments). If the patient is non-responsive to medical therapy, splenectomy may be required.

Evaluation of the patient by a hematologist with experience in the management of hairy cell leukemia may enable the reason for the patient’s lack of response to be understood. To avoid being retreated too early or unnecessarily, it may be helpful to consult an HCL expert at one of our Centers of Excellence.