Contributions
Abstract: P655
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Efficacy of cladribine tablets (CT) was demonstrated in the 2-year (96-week) CLARITY study. Lymphopenia was the most commonly reported adverse event, consistent with the mechanism of action of CT.
Objective: To investigate absolute lymphocyte counts up to 312 weeks and B and T cell subsets up to 240 weeks after the first administered dose of CT, in patients with RRMS receiving 2 annual courses of CT (3.5mg/kg) followed by no further active treatment.
Methods: Data from patients randomised to CT 3.5mg/kg over 2 years in CLARITY or CLARITY Extension including time spent in the PREMIERE registry (N=685) were pooled to provide long-term follow-up data.
Results: At baseline, median absolute lymphocyte count (ALC) was 1.86×109/L. During Year (Y)1, ALC reached nadir at 9 weeks post-treatment with CT 3.5mg/kg (1.00×109/L) and then gradually increased. During Y2, ALC reached nadir at Week (Wk) 55 (0.81×109/L), recovered to the normal range (≥1.00×109/L) by the end of Y2 (Wk96), and continued to increase thereafter. ALC had returned to the normal range in 75% of patients by Wk144. Median CD4+ lymphocytes were 851 cells/µL at baseline. After treatment in Y1, CD4+ reached nadir at Wk16 (385 cells/µL) and then gradually increased. CD4+ reached nadir after Y2 treatment at Wk60 (292 cells/µL). Values then gradually recovered, reaching the threshold of 350 cells/µL by approximately Wk120, continuing to improve thereafter. Median CD8+ lymphocytes at baseline were 378 cells/µL. CD8+ reached Y1 nadir at Wk16 (239 cells/µL), then gradually increased, and Y2 nadir was reached at Wk72 (232 cells/µL). CD8+ recovered quickly after treatment and never dropped below the threshold of 200 cells/µL at any time in the 240-week observation period. Median CD19+ lymphocytes were 205 cells/µL at baseline. After Y1 treatment, CD19+ reached nadir at Wk9 (18 cells/µL) and after Y2 treatment at Wk52 (31 cells/µL). CD19+ then gradually recovered, reaching the threshold of 100 cells/µL by the end of Y2 (Wk96), continuing to improve thereafter.
Conclusion: Lymphocyte recovery begins soon after CT treatment, with ALC, CD19+ B cells and CD4+ T cells reaching threshold values by 7.5 months, 12 months and 18 months, respectively, after the last dose in Y2. CD8+ cells never dropped below the threshold value.
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).
PS-S: 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.
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.
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.
Abstract: P655
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Efficacy of cladribine tablets (CT) was demonstrated in the 2-year (96-week) CLARITY study. Lymphopenia was the most commonly reported adverse event, consistent with the mechanism of action of CT.
Objective: To investigate absolute lymphocyte counts up to 312 weeks and B and T cell subsets up to 240 weeks after the first administered dose of CT, in patients with RRMS receiving 2 annual courses of CT (3.5mg/kg) followed by no further active treatment.
Methods: Data from patients randomised to CT 3.5mg/kg over 2 years in CLARITY or CLARITY Extension including time spent in the PREMIERE registry (N=685) were pooled to provide long-term follow-up data.
Results: At baseline, median absolute lymphocyte count (ALC) was 1.86×109/L. During Year (Y)1, ALC reached nadir at 9 weeks post-treatment with CT 3.5mg/kg (1.00×109/L) and then gradually increased. During Y2, ALC reached nadir at Week (Wk) 55 (0.81×109/L), recovered to the normal range (≥1.00×109/L) by the end of Y2 (Wk96), and continued to increase thereafter. ALC had returned to the normal range in 75% of patients by Wk144. Median CD4+ lymphocytes were 851 cells/µL at baseline. After treatment in Y1, CD4+ reached nadir at Wk16 (385 cells/µL) and then gradually increased. CD4+ reached nadir after Y2 treatment at Wk60 (292 cells/µL). Values then gradually recovered, reaching the threshold of 350 cells/µL by approximately Wk120, continuing to improve thereafter. Median CD8+ lymphocytes at baseline were 378 cells/µL. CD8+ reached Y1 nadir at Wk16 (239 cells/µL), then gradually increased, and Y2 nadir was reached at Wk72 (232 cells/µL). CD8+ recovered quickly after treatment and never dropped below the threshold of 200 cells/µL at any time in the 240-week observation period. Median CD19+ lymphocytes were 205 cells/µL at baseline. After Y1 treatment, CD19+ reached nadir at Wk9 (18 cells/µL) and after Y2 treatment at Wk52 (31 cells/µL). CD19+ then gradually recovered, reaching the threshold of 100 cells/µL by the end of Y2 (Wk96), continuing to improve thereafter.
Conclusion: Lymphocyte recovery begins soon after CT treatment, with ALC, CD19+ B cells and CD4+ T cells reaching threshold values by 7.5 months, 12 months and 18 months, respectively, after the last dose in Y2. CD8+ cells never dropped below the threshold value.
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).
PS-S: 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.
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.
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.