DX71
Reduction of Lymphopenia by Cladribine Tablets Under Retreatment Guidelines: A Long-Term Follow-Up Analysis of Patients in the ORACLE-MS Study

Thursday, May 25, 2017
B2 (New Orleans Convention Center)
Thomas Leist, MD , Thomas Jefferson University, Philadelphia, PA
Giancarlo Comi, MD , University Vita-Salute San Raffaele, Milan, Italy
Mark S Freedman, MD , University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
Bruce AC Cree, MD, PhD , Neurology, University of California, San Francisco, CA
Patricia K Coyle, MD , Stony Brook University, Stony Brook, NY
Hans-Peter Hartung, MD , Department of Neurology, Medical Faculty, Heinrich-Heine University, Dusseldorf, Germany
Patrick Vermersch, MD , University of Lille, Lille, France
Elke Sylvester, MD , Merck KGaA, Darmstadt, Germany
Doris Damian, PhD , EMD Serono, Inc., Billerica, MA
Fernando Dangond, MD , EMD Serono, Inc., Billerica, MA
Mary Lee, NA , Caudex, New York, NY
Michele Springer, BA , Caudex, New York, NY
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Background: In the ORACLE-MS study in patients with a first demyelinating event, treatment with two short courses at the beginning of two consecutive years of cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of CDMS compared with placebo. Guidelines implemented in ORACLE-MS restricted cladribine retreatment to patients with Grade 0 or 1 lymphopenia at the beginning of the second year course. 

Objectives: To assess severity and recovery from lymphopenia in the ORACLE-MS long-term follow-up (LTFU), among patients treated with cladribine tablets during the ORACLE-MS initial treatment period (ITP). 

Methods: ORACLE-MS patients were aged 18-55 years with a first clinical demyelinating event within 75 days before screening, ≥2 clinically silent lesions of ≥3 mm on a T2-weighted brain scan, and an EDSS score of ≤5. Patients were randomized (1:1:1) to placebo, cladribine tablets 3.5 mg/kg or cladribine tablets 5.25 mg/kg of bodyweight (cumulative over 2 years). Patients who did not convert to McDonald MS during the ITP did not receive any additional study medication during the LTFU, but were followed for safety and efficacy evaluations for 48 weeks after the end of ITP, or until McDonald MS or CDMS conversion.

Results: CTCAE Grade 3/4 lymphopenia occurred in 46 (22.3%) and 74 (36.5%) patients receiving cladribine tablets 3.5 mg/kg and 5.25 mg/kg, respectively (ITP; up to 2 consecutive years). Grade 4 lymphopenia was limited to 3 patients (1 in 3.5 mg/kg and 2 in 5.25 mg/kg). In the 3.5 mg/kg group, 78 patients completed the 2 years of ITP, and 36 of these entered the LTFU and received no further treatment. At LTFU baseline, none of these 36 patients had Grade 3/4 lymphopenia, 4 patients had Grade 2 lymphopenia. All of these recovered to Grade 0 or 1 by LTFU week 13. 

Conclusions: In ORACLE-MS, the occurrence of CTCAE Grade ≥3 lymphopenia was dose related. The retreatment guidelines introduced in ORACLE-MS appeared to limit the occurrence and duration of Grade 3/4 lymphopenia. All patients recovered to Grade 0 or 1 by Week 13 in the long-term follow-up period.

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