Approaches to Frontline Therapy in HCL

Transcript:Gary J. Schiller, MD: We have several new drugs for the treatment of hairy cell leukemia. For many years, the purine nucleoside analogs have been the mainstay of therapy, and we’ve had several of them to use in the management of hairy cell leukemia. But now we have some other alternatives for patients with relapsed disease. We have the monoclonal antibodies, rituximab, moxetumomab pasudotox, as well as BRAF inhibitors.

The first issue is the timing of therapy. Not every patient who has a diagnosis of hairy cell leukemia warrants therapy immediately at diagnosis. The driver of therapy is bone marrow suppression, neutropenia particularly, that’s the major feature of hairy cell leukemia. Generally, patients do not have lymphocytosis, so that would not be a driver. Sometimes they have anemia and thrombocytopenia. That would be a potential driver of therapy. They generally do not have lymphadenopathy. And although most patients have splenomegaly, the splenomegaly is not sufficient to be a driver of therapy either. So there are some patients for whom a watchful waiting is appropriate, as you would do with any lymphoproliferative disease. But if you choose that pathway, then you do need to really watch the patients and wait for the trigger. And the trigger to me is neutropenia with an ANC [absolute neutrophil count] of less than 500 to 1000. That usually is the thing that would push my button to treat a patient.

Still, the upfront therapy is a purine nucleoside drug. And my personal choice is cladribine. However, pentostatin is also an effective drug. Fludarabine is effective as well, although fludarabine comes with so many potential adverse effects such as marrow suppression and secondary leukemia that it doesn’t enter into my registry. But both cladribine and pentostatin are effective. They have not been compared head-to-head, they never will be, and people have different preferences.

Cladribine is typically given in an either bolus fashion daily for 5 days or by continuous infusion for 7, and pentostatin is given every 2 weeks typically. But cladribine could also be given potentially every week or every 2 weeks. It’s just that we typically don’t do that. And so people who treat hairy cell leukemia have their preference. The time to the induction of remission may be faster with cladribine, but the time to induction of severe neutropenia and marrow suppression will also be faster.

I could imagine some patient, a frailer, older person, somebody for whom a continuous intravenous infusion is not appropriate—somebody for whom a daily subcutaneous or intravenous bolus would also not be appropriate, somebody who is more housebound—who might be an appropriate candidate for a treatment that may work, in a way slower, but is convenient to give because it doesn’t require quite that degree of intervention.

Transcript Edited for Clarity