Personalized Cladribine Dosing for Multiple Sclerosis

Kimberley Allen-Philbey, PhD candidate

Subcutaneous cladribine personalized dosing (CPD) seems to be well-tolerated in patients with relapsing multiple sclerosis (RMS), with efficacy in line with oral cladribine (Mavenclad; EMD Serono) trial data, according to data from a recent study.

First author Kimberley Allen-Philbey, PhD candidate, Barts MS Center, London, presented these findings at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, February 25-27. Allen-Philbey and colleagues found that over the follow-up period, 1 myocardial infarction, 1 breast cancer, 1 pulmonary embolism, and 3 severe allergic skin reactions without long-term sequelae occurred with CPD. Death occurred in 2 severely disabled patients with MS, 1 from influenza and 1 from encephalitis. Lymphopenia of at least grade 3 occurred in 7% of patients. 

In terms of efficacy, EDSS remained stable or improved in 99 (82%) patients with MS with baseline and 2-year follow-up data. Of the 23 patients with MS that had elevated baseline cerebrospinal fluid neurofilament light (median, 652 pg/mL; interquartile range [IQR], 458-1063), 22 had normal levels at follow-up (median, 344 pg/mL; IQR, 186-505).

NeurologyLive spoke with Allen-Philbey to learn more about off-label cladribine and its advantages in patients with MS. She also spoke about the benefits of using personalized dosing.

NeurologyLive: What prompted you to look into CPD?

Kimberley Allen-Philbey: So, we know that only about 1 in 5 patients will have a benign course of MS, which means that the majority of patients with MS will accumulate progressive disability over time. MS-related disability can impact people's daily activities from being able to function independently to their employment status, and also relationships. So, it's important that disease modifying treatment (DMT) is an option for people with MS across the disability spectrum—from early stages, right through to advanced MS. Until fairly recently, we know that there have been no or even limited treatment options, especially for patients with progressive MS.

How does this subcutaneous, personalized cladribine dosing differ from oral cladribine, and what advantages does it offer?

So, we've treated 250 people with MS with subcutaneously injected cladribine. Essentially, it is the same compound. It's the mode of administration which differs, and the speed. Being able to offer cladribine on an off-label basis has meant that we've been able to offer patients treatment options that wouldn't previously have access to it. And so, by detecting disease activity, for example, using magnetic resonance imaging (MRI) indices, and neurofilaments, or lumbar puncture, we've been able to provide treatments patients who have evidence of disease activity, but who otherwise wouldn't have been eligible for a licensed disease modifying treatment.

The mode of administration is very convenient for patients. Even though it is an injection, patients only come into the center for a few minutes. Many patients have reported that they are actually quite surprised by how underwhelming the experience can be for them. And in terms of the monitoring requirements, those are also very minimal. And so, it is a well-favored DMT option for patients with MS.

Oral cladribine is taken in 2 treatment cycles. Our treatment schedule is adapted to make it personalized for patients. So, by being personalized, we mean that it's adapted to the patient's body weight, and also to their lymphocyte counts. By this personalization, we've ensured that it's as safe as possible a treatment for patients. So, we were able to avoid severe lymphopenia using this adaptive, personalized investing in 93% of patients with MS, which we're very pleased with.

Transcript edited for clarity. For more coverage of ACTRIMS Forum 2021, click here.

REFERENCE

Allen-Philbey K, De Trane S, Stennett A, et al. Cladribine personalised dosing to treat active multiple sclerosis - follow-up in 250 patients. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Abstract P160.