Contributions
Abstract: P666
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: The CLARITY and CLARITY Extension studies demonstrated the efficacy of cladribine tablets in patients with relapsing multiple sclerosis. The most common adverse event was lymphopenia, consistent with the mechanism of action of cladribine tablets.
Objective: To evaluate whether lymphopenia persists following treatment and re-treatment with cladribine tablets 3.5 mg/kg.
Methods: Lymphopenia by grade (National Cancer Institute Common Terminology Criteria for Adverse Events v3.0) for patients who were randomised to cladribine tablets 3.5mg/kg in the two-year CLARITY study and re-randomised to cladribine tablets 3.5mg/kg in the two-year CLARITY Extension study
(7 mg/kg cumulative dose over 4 years; N=186) are reported. Patients with Grade 0 lymphopenia
(≥1.0×109 cells/L) before the first course of cladribine tablets and Grade 0 or 1 (≥0.8×109 cells/L) prior to administration of all subsequent courses in Years 2, 3 and 4 were included in the analysis, according to re-treatment guidelines.
Results: 176 patients were Grade 0 at the start of CLARITY and 167 patients were Grade 0 or 1 at the start of CLARITY Extension. Grade 3 lymphopenia was observed in 1% of patients at Week 13 in Year 1, and in 7%, 11% and 12% of patients at Week 12 in Years 2, 3 and 4, respectively. By Week 24 in each of Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 4%, 4% and 4% of patients, respectively. By Week 36 in each of Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 2%, 2% and 2% of patients, respectively. By Week 48 in each year, Grade 3 lymphopenia was only observed in Year 2 (1% of patients). Occurrence of Grade 3 lymphopenia was reported in < 18% of patients at any single time point. No patients had Grade 4 lymphopenia at the end of any of the four treatment years.
Conclusions: In patients who were treated according to re-treatment guidelines i.e. having lymphocyte counts ≥1.0×109/L before the first course and ≥0.8×109/L before up to 3 subsequent annual courses of cladribine tablets (up to 7 mg/kg cumulative dose), no patients experienced Grade 4 lymphopenia at the end of any treatment year, and Grade 3 lymphopenia was uncommon. Results of this study demonstrate the effectiveness of lymphocyte-based re-treatment criteria in minimising the incidence of severe, sustained lymphopenia during four years' treatment with cladribine tablets.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
SC has received honoraria for lectures/consultations from Merck Serono, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
GC has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptors, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec FivePrime, GlaxoSmithKline, GW Pharma, Merck,, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood, and Novartis; and has received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.
PR has received honoraria for lectures/steering committee meetings from Merck, Biogen Idec, Bayer Schering Pharma, Boehringer-Ingelheim, Sanofi-Aventis, Genzyme, Novartis, Teva Pharmaceutical Industries, and Serono Symposia International Foundation.
PSS has served on advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals, and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Teva, GSK, and Novartis; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis. His department has received research support from Biogen, Merck, Teva, Novartis, Roche, and Genzyme.
PV has received honoraria or consulting fees from Biogen, Sanofi-Genzyme, Bayer, Novartis, Merck, GSK, Roche and Almirall; and research support from Biogen, Sanofi-Genzyme, Bayer, and Merck.
FD is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.
CH is an employee of Merck KGaA, Darmstadt, Germany.
Abstract: P666
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: The CLARITY and CLARITY Extension studies demonstrated the efficacy of cladribine tablets in patients with relapsing multiple sclerosis. The most common adverse event was lymphopenia, consistent with the mechanism of action of cladribine tablets.
Objective: To evaluate whether lymphopenia persists following treatment and re-treatment with cladribine tablets 3.5 mg/kg.
Methods: Lymphopenia by grade (National Cancer Institute Common Terminology Criteria for Adverse Events v3.0) for patients who were randomised to cladribine tablets 3.5mg/kg in the two-year CLARITY study and re-randomised to cladribine tablets 3.5mg/kg in the two-year CLARITY Extension study
(7 mg/kg cumulative dose over 4 years; N=186) are reported. Patients with Grade 0 lymphopenia
(≥1.0×109 cells/L) before the first course of cladribine tablets and Grade 0 or 1 (≥0.8×109 cells/L) prior to administration of all subsequent courses in Years 2, 3 and 4 were included in the analysis, according to re-treatment guidelines.
Results: 176 patients were Grade 0 at the start of CLARITY and 167 patients were Grade 0 or 1 at the start of CLARITY Extension. Grade 3 lymphopenia was observed in 1% of patients at Week 13 in Year 1, and in 7%, 11% and 12% of patients at Week 12 in Years 2, 3 and 4, respectively. By Week 24 in each of Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 4%, 4% and 4% of patients, respectively. By Week 36 in each of Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 2%, 2% and 2% of patients, respectively. By Week 48 in each year, Grade 3 lymphopenia was only observed in Year 2 (1% of patients). Occurrence of Grade 3 lymphopenia was reported in < 18% of patients at any single time point. No patients had Grade 4 lymphopenia at the end of any of the four treatment years.
Conclusions: In patients who were treated according to re-treatment guidelines i.e. having lymphocyte counts ≥1.0×109/L before the first course and ≥0.8×109/L before up to 3 subsequent annual courses of cladribine tablets (up to 7 mg/kg cumulative dose), no patients experienced Grade 4 lymphopenia at the end of any treatment year, and Grade 3 lymphopenia was uncommon. Results of this study demonstrate the effectiveness of lymphocyte-based re-treatment criteria in minimising the incidence of severe, sustained lymphopenia during four years' treatment with cladribine tablets.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
SC has received honoraria for lectures/consultations from Merck Serono, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
GC has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptors, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
GG has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec FivePrime, GlaxoSmithKline, GW Pharma, Merck,, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood, and Novartis; and has received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.
PR has received honoraria for lectures/steering committee meetings from Merck, Biogen Idec, Bayer Schering Pharma, Boehringer-Ingelheim, Sanofi-Aventis, Genzyme, Novartis, Teva Pharmaceutical Industries, and Serono Symposia International Foundation.
PSS has served on advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals, and GSK; on steering committees or independent data monitoring boards in trials sponsored by Merck, Teva, GSK, and Novartis; has received speaker honoraria from Biogen Idec, Merck Serono, Teva, Sanofi-Aventis, Genzyme, and Novartis. His department has received research support from Biogen, Merck, Teva, Novartis, Roche, and Genzyme.
PV has received honoraria or consulting fees from Biogen, Sanofi-Genzyme, Bayer, Novartis, Merck, GSK, Roche and Almirall; and research support from Biogen, Sanofi-Genzyme, Bayer, and Merck.
FD is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.
CH is an employee of Merck KGaA, Darmstadt, Germany.