Early Experience with Cladribine Tablets in an Aging Patient Population

Background: Cladribine, a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes, may disrupt the central immune cascade in persons with multiple sclerosis (MS). Cladribine tablets are a short-course oral disease-modifying drug (DMD) administered in four four-to-five-day courses over two years. Cladribine tablets are indicated for the treatment of adults with relapsing forms of MS based on data from pivotal clinical trials, including the phase 3 study, CLARITY, and its extension.

Objectives: Our study aims to present real-world experience in aging MS patients treated with cladribine. Understanding the benefit/risk profile of using a non-continuous immunosuppressive DMD in this population is of utmost importance given immunosenescence and the increased risk of comorbidities with age. Outcomes presented include patient characteristics at treatment initiation, previous DMD use, safety, lymphocyte counts, and preliminary efficacy data.

Methods: Prospective and retrospective chart review.

Results: We report on 48 patients who have initiated therapy with cladribine tablets. Median age at cladribine initiation was 51.6 years (range 29-72) with median disease duration of 12 years (range 1-26). As of the data cutoff 3/1/22, 34 patients (71%) completed course 1 & 2, while 14 patients (29%) completed course 1, but had not yet reached course 2. In this cohort, the mean number of relapses in the 12 months prior to cladribine initiation is 0.875, and the mean number of relapses since cladribine initiation is 0.32.

Two patients (4%) discontinued therapy prior to completing course 2. One patient discontinued due to disease activity and resumed their prior treatment, and one patient discontinued due to an asymptomatic fungal pulmonary infection incidentally found on routine thoracic MRI. 80% of patients experienced lymphopenia. The grades of lymphopenia were similar to those observed in CLARITY and will be further depicted in the poster.

Overall, cladribine tablets were well tolerated. Headache, fatigue, upper respiratory tract infection and urinary tract infection occurred in ≥ 5% of patients.

Conclusions: In this cohort of patients initiating therapy with cladribine tablets in a real-world setting, the treatment was well-tolerated. There were no new safety signals. The side effect profile was consistent with that seen in the clinical trial program, even in an aging patient population where co-morbid conditions and immunosenescence may increase. Owing to short follow-up time, it was not possible to assess long-term outcomes. Ongoing follow-up will further expand on these results as more patients complete their full treatment course. The complete and most current cohort analysis to be presented in the poster on June 2, 2022.