Monitoring Response & Initiating Second-Line Therapy in HCL

Transcript: Leslie Andritsos, MD: For patients who receive a complete remission with therapy, they will not need very frequent follow-up. But one of the things to consider is that these patients are going to be very immunocompromised and need to be monitored for infection. So I typically will see patients about every 3 months during which times I will check a CBC [complete blood count], routine chemistry panel. I typically will check a CD4 count at the end of therapy to see how generally immunocompromised patients are, and also soluble IL-2 [interleukin-2] receptor level testing, which gives a good post-treatment baseline to see if those values start to rise, they may be an early indication of disease progression. Once patients have recovered their CD4 counts, I typically will discontinue their antibiotic prophylaxis such as HSV, VVC prophylaxis, and monitor maybe once every 6 months to once a year, as long they’re doing well.

Gary J. Schiller, MD: Bone marrow biopsy is often useful to make the diagnosis, although if you have a reasonable index of suspicion, you can make the diagnosis from peripheral blood. I think what happens, however, in real life, is that in the evaluation of neutropenia or some other cytopenia, a bone marrow biopsy is done. Now, hopefully for a patient with neutropenia, when the bone marrow biopsy is submitted, the doctor requests evaluation for hairy cell leukemia, large granular lymphocytosis, and perhaps some other diseases that would not automatically make themselves manifest to a pathologist who’s merely looking at a bone marrow aspirate.

The big question is whether you ever need to do the bone marrow again, and I might be one of the naysayers in the world of hairy cell leukemia doctors. There are not that many of us, you could have us all over to not even your living room, everybody can probably fit in your kitchen. There would be enough room for us. But to me, the endpoint of successful therapy is recovery of blood counts. So I don’t need to see normalization of marrow. Normalization of marrow with resolution of residual hairy cells, that can take a minimum of 3 months after your initial upfront management. So whether one needs to look is a question to me, and if I see normalization or near normalization of blood counts, I have no particular need to establish on bone marrow biopsy that a complete remission has been obtained.

The timing of second-line therapy really depends on the timing of relapse. If it has taken many years for disease to recur, then the same therapy as was given initially is very likely to achieve a favorable outcome. So a patient who’s had cladribine or pentostatin who took 5 or 10 years to sustain recurrent neutropenia, and in that case, often bone marrow evidence of recurrent disease is very likely to have response to single-agent purine nucleoside drug. For the patients who have an early relapse, which I define in my practice as within 2 or 3 years of achieving initial response, you have several options. One can treat again with a purine nucleoside drug, expecting a high likelihood of remission but a duration of remission that is likely to be shorter than the first remission duration; use of an entirely different agent such as rituximab; or combination therapy of a purine nucleoside analog and rituximab. In this second-line setting, it’s not yet quite established that the newer drugs, such as a BRAF inhibitor or moxetumomab pasudotox, might enter the therapeutic paradigm.

Transcript Edited for Clarity