Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Department of Neurology, Stony Brook University, Stony Brook, NY, United States.
Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.
Cladribine tablets (CladT) preferentially reduce B and T lymphocyte levels. As aging is associated with a decline in immune function, the effect of CladT on lymphocyte levels may differ by age. This analysis combined data from the Phase 3 CLARITY, CLARITY Extension, and ORACLE-MS studies to examine the effect of age (≤50 or >50 years) on lymphopenia following CladT 3.5 mg/kg (CladT3.5; cumulative dose over 2 years) treatment over 96 weeks. Both CladT3.5 and placebo were given over Weeks 1 and 5 (Year 1 treatment) and Weeks 48 and 52 (Year 2 treatment) from the start of the studies. Absolute lymphocyte count (ALC) and levels of lymphocyte subsets were examined in 1564 patients (Age ≤50 [placebo: N=566; CladT3.5: N=813]; Age >50 [placebo: N=75; CladT3.5: N=110]). In both age groups, following CladT3.5 treatment, nadir for ALC occurred at Week 9 (8 weeks following start of Year 1 treatment) and Week 55 (7 weeks following start of Year 2 treatment) of the 96-week period; for CD19+ B lymphocytes, nadir occurred at Week 9 (Year 1) and Week 52 (Year 2). For CD4+ T lymphocytes, nadir occurred at Week 16 (Year 1) in both age groups, and at Weeks 60 and 72 (Year 2) in the Age ≤50 and >50 groups, respectively. Nadir for CD8+ T lymphocytes occurred at Week 16 (Year 1) and Week 72 (Year 2) in the Age ≤50 group and levels remained in the normal range; nadir occurred at Week 9 (Year 1) and Week 96 (Year 2) in the Age >50 group. Lymphocyte recovery began soon after nadir following CladT3.5 treatment and median levels reached normal range by end of the treatment year in both age groups. By Week 96, ~25% of patients treated with CladT3.5 reported ≥1 episode of Grade ≥3 lymphopenia (Gr≥3L). The rate of certain infections was numerically higher in older versus younger patients who experienced Gr≥3L. In conclusion, CladT3.5 had a similar effect on ALC and lymphocyte subsets in both younger and older patient groups.
克拉屈滨片（CladT）优先降低 B 和 T 淋巴细胞水平。由于衰老与免疫功能下降有关，克拉屈滨对淋巴细胞水平的影响可能因年龄而异。本分析结合了 3 期 CLARITY、CLARITY 扩展和 ORACLE-MS 研究的数据，以检查年龄（≤50 岁或>50 岁）对克拉屈滨 3.5mg/kg（克拉屈滨 3.5；2 年内累积剂量）治疗 96 周后淋巴细胞减少的影响。克拉屈滨 3.5 和安慰剂均在研究开始的第 1 周和第 5 周（第 1 年治疗）以及第 48 周和第 52 周（第 2 年治疗）给予。在 1564 名患者（年龄≤50 [安慰剂：N=566；克拉屈滨 3.5：N=813]；年龄>50 [安慰剂：N=75；克拉屈滨 3.5：N=110]）中检查了绝对淋巴细胞计数（ALC）和淋巴细胞亚群水平。在两个年龄组中，克拉屈滨 3.5 治疗后，ALC 的最低点出现在第 9 周（第 1 年治疗开始后 8 周）和第 55 周（第 2 年治疗开始后 7 周）的 96 周期间；对于 CD19+B 淋巴细胞，最低点出现在第 9 周（第 1 年）和第 52 周（第 2 年）。对于 CD4+T 淋巴细胞，两组的最低点均出现在第 16 周（第 1 年），年龄≤50 岁组的最低点出现在第 60 周和第 72 周，年龄>50 岁组的最低点出现在第 60 周和第 72 周。CD8+T 淋巴细胞的最低点出现在第 16 周（第 1 年）和第 72 周（第 2 年）的年龄≤50 岁组，且水平保持在正常范围内；年龄>50 岁组的最低点出现在第 9 周（第 1 年）和第 96 周（第 2 年）。克拉屈滨 3.5 治疗后，淋巴细胞最低点后不久开始恢复，两组患者的中位数水平在治疗年末均恢复到正常范围。在第 96 周时，约 25%接受克拉屈滨 3.5 治疗的患者报告了≥1 次≥3 级淋巴细胞减少症（Gr≥3L）事件。与经历 Gr≥3L 的年轻患者相比，年龄较大的患者发生某些感染的比率在数值上更高。总之，克拉屈滨 3.5 在年轻和老年患者组中对 ALC 和淋巴细胞亚群均有相似的影响。
