Personalised dosing of cladribine for people with multiple sclerosis (P3.400)

Objective: To address a critical issue - severe treatment-induced lymphopenia - during the European Medicines Agency (EMA)-assessment of cladribine, a highly effective disease modifying treatment (DMT) for people with multiple sclerosis (pwMS). Background: Oral cladribine (Mavenclad®) has recently been licensed by the EMA as a DMT for pwMS with high disease activity. Our team have been using subcutaneously injected cladribine (Litak®) to treat pwMS for more than three years. Design/Methods: Litak® was offered to pwMS with (i) clinical and (ii) MRI and/or cerebrospinal fluid neurofilament light chain level-derived disease activity. Litak® 30–40mg was administered in week 1 and - pending lymphocyte count - up to 30mg in week 5. Results: Seventy-six pwMS (mean age 45 years; disease duration 10 years) underwent treatment; 35/76 (23 female) were followed up for at least four months; 14/34 pwMS (39%) were treatment-naive; 20/34 pwMS (59%) switched from licensed DMT, mainly fingolimod (50%). Median EDSS at baseline was 5 (range 1–7.5), and 5.5 (range 1–8) after a median of 10 months (range 5–28). Four pwMS experienced a total of six relapses median of 12 months (range 3–23) post treatment. In people with progressive MS (n=18) median EDSS was 5.5 (2–7.5) at baseline and 6 (2.5–7.5) after median of 9.5 (range 5–18) months. Personalised dosing led to lymphopenia (WHO grade 1–2) in 50%, however prevented lymphopenia below 0.5*10 9 /L in 75/76 pwMS. Cladribine was well tolerated with very few treatment-related adverse events observed. Conclusions: Personalised dosing of cladribine was very well tolerated and avoided severe lymphopenia in all but one pwMS. Study Supported by: This study was supported by an ECTRIMS Clinical Training Fellowship to ZM, and a grant from the Multiple Sclerosis Society of Great Britain u0026 Northern Ireland. Disclosure: Dr. Mao has nothing to disclose. Dr. Alvarez-Gonzalez has nothing to disclose. Dr. Yildiz has nothing to disclose. Dr. Allen-Philbey has nothing to disclose. Dr. Turner has nothing to disclose. Dr. Gnananpavan has nothing to disclose. Dr. Marta has nothing to disclose. Dr. Mathews has nothing to disclose. Dr. Giovannoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for participating on Advisory Boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees from: Abbvie, Almirall, Atara Bio, Biogen, Sanofi-Genzyme, Genentech, GSK, Merck, Novartis. Dr. Giovannoni has received personal compensation in an editorial capacity for Elsevier as Editor of MSARDs. Dr. Giovannoni has received research support from Takeda. Dr. Baker has received compensation for serving on the Board of Directors of Canbex. Dr. Baker holds stock and/or stock options in Canbex, which sponsored research in which Dr. Baker was involved as an investigator. Dr. Baker has received research support from Sanofi-Genzyme. Dr. Schmierer has nothing to disclose.