Individualized Dosing of Cladribine Cuts Lymphopenia Risk

Andrew N. Wilner, MD

Disclosures

June 06, 2018

Introduction

While attending the 2018 American Academy of Neurology meeting in Los Angeles, California, Medscape contributor Andrew N. Wilner, MD, interviewed Kimberley Allen-Philbey about her research into personalized treatment of multiple sclerosis (MS).[1] Allen-Philbey is a research assistant at the Royal London Hospital in England and is currently working at Massachusetts General Hospital in Boston.

Wilner: Oral cladribine was recently approved as a treatment for relapsing-remitting MS in Europe but not yet in the United States. That makes this a particularly interesting topic for us here in the United States. Tell me about personalized dosing. Why is that important?

Allen-Philbey: Based on the phase 2 and 3 trials,[2,3,4,5] it was clear that lymphopenia is one of the adverse effects of cladribine. To account for that and given that the safety of patients is paramount, we adjusted the dose of cladribine according to each patient’s baseline lymphocyte count. We subsequently measured lymphocyte counts at week zero, week four, and then during the second treatment cycle which takes place during the second year.

The dose was adjusted according to not only the lymphocyte count but also the patient's weight. Again, the adjustment was extrapolated from information from the earlier clinical trials, so we modified the dose based on a weight of 90 kg. If the patient weighed more than 90 kg, the patient received an extra dose to account for the extra body mass. Our results have shown this to be successful. Fortunately, we had only one case of severe lymphopenia, with a lymphocyte count of 0.4 x 109/L.

Wilner: How many patients were in your study?

Allen-Philbey: This particular cohort included 76 patients. By now we have treated almost three times that number .

Wilner: So, only one patient had significant lymphopenia. Did that patient have any infections related to the lymphopenia?

Allen-Philbey: No, the patient did not.

Wilner: The patient managed to avoid adverse clinical effects. If you had not checked the lymphocyte count, you would not have known that the patient had a lymphocyte deficit.

Allen-Philbey: That’s correct. With personalized dosing, you can adjust the amount of cladribine you are giving. We found it to be a successful protocol.

Wilner: Do you plan to continue to do this with future patients who take cladribine?

Allen-Philbey: Absolutely. This is the protocol we are using at Mass General with subcutaneous cladribine. The cladribine formulation that was recently licensed is the oral form. For this study, we used subcutaneous cladribine, which has a high—100%—bioavailability. This is what we are using now and will continue to use.

We have almost 200 patients now who are being treated with this protocol, and it has been given off-label to patients throughout the UK, to patients in our East London service, and also to patients who are referred in. So protocols are being established that can be used in other centers as well.

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