Author Of 1 Presentation
P0872 - Efficacy and Safety of Intravenous and Subcutaneous Cladribine in Relapsing and Progressive Multiple Sclerosis: a 24-year retrospective (ID 1243)
Abstract
Background
Intravenous and subcutaneous cladribine has been used in multiple sclerosis since 1993. While oral cladribine is now approved by the EMA and FDA, the dosing of intravenous and subcutaneous cladribine is equivalent to twice that given with oral cladribine and in half the time. Based upon its mechanism of action, prolonged effect, and significant CNS penetration, we felt MS patients with aggressive or progressive disease would be ideal candidates for this medication and have been using cladribine since 1995.
Objectives
This study reports the efficacy and safety of a large cohort of multiple sclerosis (MS) patients receiving intravenous or subcutaneous cladribine. The primary objective is assessing the clinical outcomes. The secondary objective is assessing hematologic abnormality, infection, and cancer rates.
Methods
This is a retrospective cohort study of relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive (PPMS) MS patients treated with intravenous or subcutaneous cladribine at the Rush Multiple Sclerosis Center from January 1995 to May 2019. Each round of cladribine was 0.7 mg/kg given over 5 days. Subsequent rounds were given once the total white blood cell count was normal. Full course consists of 4 rounds, or a total dose of 2.8 mg/kg (equivalent to 5 mg/kg of oral cladribine). Additional intravenous or subcutaneous doses were administered based upon new clinical or MRI activity.
Results
There were 247 patients in the cohort with 2198 patient-years of follow-up. Mean age of patients and disease duration at the time of first dose was 42.9 and 11.2 years, respectively. Mean follow-up after the first dose was 7.6 years. RRMS and active SPMS comprised 51.2% while non-active SPMS and PPMS made up 43.9% of patients. A full course was completed by 77.3% of patients. At least one additional dose of cladribine was given to 24.6% of patients at a mean of 3.5 years after the fourth round. Clinical outcomes were 46.4% had sustained clinical improvement, 37% were stable, and 16.7% continued to progress. Mean duration for stability or improvement after a full course was 2.3 and 3.6 years, respectively. Mean nadir of the white blood cell count was 3.3 K/uL. Mean maximum time to Grade 1 leukopenia was 0.6 months. Mean nadir lymphocyte count was 0.27 K/uL. Mean maximum time to Grade 0-1 lymphopenia was 8.7 months. For serious adverse events, there were 13 cases of cancer (0.59 cases per 100 patient-years), 3 serious infections, 6 cases of herpes zoster, 2 cases of myelodysplastic syndrome, and 14 deaths.
Conclusions
Intravenous and subcutaneous cladribine resulted in most patients having temporary clinical stability or improvement of their most disabling MS symptoms. Most patients experienced a transient leukopenia and lymphopenia. Overall, the treatment was well tolerated with no unexpected serious adverse events.