The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London
Neuroscience and Trauma

Author Of 1 Presentation

Observational Studies Poster Presentation

P0850 - Cladribine personalised dosing to treat multiple sclerosis: observations in 208 patients (ID 1521)

Abstract

Background

Oral cladribine (Mavenclad®) was approved as a disease-modifying treatment (DMT) for highly active relapsing multiple sclerosis (RMS) in August 2017. We have treated a large cohort of people with MS (pwMS) using a personalised dosing schedule of subcutaneous cladribine (Litak®) (CPD) since 2014.

Objectives

To report safety and efficacy of cladribine personalised dosing (CPD) as an immunotherapy in people with multiple sclerosis.

Methods

CPD was offered to pwMS irrespective of their disease course, provided they had MRI-detectable inflammatory activity (gadolinium-enhancing T1 and/or more T2 lesions over past ≤2 years) or an elevated neurofilament light chain (NfL) level in their cerebrospinal fluid (CSF). Litak® 10 mg was given on three consecutive days (four in pwMS >90kg) during week 1. Based on total lymphocyte count at week 4, patients were given another 0-3 doses at week 5. A second cycle of CPD was administered 11 months later. Follow-up included recording of adverse events and relapses, annual EDSS, 9-hole-peg, Timed-25-foot-walking, Symbol-Digit-Modalities tests, and full blood counts. Proportions of pwMS with no evidence of disease activity (NEDA), and of progression or active disease (NEPAD), were calculated where complete clinical datasets were available.

Results

208 pwMS (100 relapsing, 108 progressive) underwent CPD. 192/208 received a second treatment cycle. Baseline age 44 (17-72) years, EDSS 0-8.5. Tolerability was very good. One myocardial infarction and one breast cancer occurred. Two severely disabled pwMS died (one influenza, one encephalitis). 12/208 had transient skin reactions. Lymphopenia ≥ grade 3 was detected in <3%. At 2 years, 66% (95% CI 49%, 80%) of pwRMS (total n=38) had NEDA and 62% (95% CI 32%, 86%) of pwPMS (total n=13) NEPAD. Of 23 pwMS with elevated baseline CSF-NfL, 22 had normal levels at follow-up. Median CSF-NfL levels were 652 pg/mL (IQR 458-1063) and 344 pg/mL (IQR 186-505) at baseline and follow-up, respectively.

Conclusions

CPD is a promising and well-tolerated alternative for pwMS not eligible for licensed DMTs. Efficacy in pwRMS was similar to controlled trial data. NEPAD rates in the proportion of pwPMS with full datasets was promising, underpinning the rationale of multi-centre, placebo-controlled trial ChariotMS (Oral cladribine to halt deterioration in people with advanced MS; n=200), starting recruitment of pwMS with EDSS 6.5-8.5 from January 2021.

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