Table 2.
Effect of disease-modifying therapies in RRMS on circulating lymphocytes
| Treatment | Degree of associated lymphopenia | Effect on circulating lymphocytes (reduction from baseline) | Lymphocyte recovery to LLN/baseline |
|---|---|---|---|
| Alemtuzumab (Lemtrada®) | Grade 3 and 4: 99.9% [18] | 1 month post-treatment initiation: |
Total lymphocytes: 6–12 months in 40 and 80% of patients (after each treatment cycle) CD4+ T cells: 12 months: 10–20% patients CD8+ T cells: similar to total lymphocyte count CD19+ B cells: 6 months in ≥ 85% [19] |
| Depletion of circulating lymphocyte to a mean of 250/mm3 and 320/mm3 blood during treatment courses 1 and 2 [18] | |||
| Cladribine (Mavenclad®) |
Phase III trial (CLARITY): Grade 3: 25.6% Grade 4: 0.7% [27] |
Phase III trial (CLARITY): 4 months post-treatment initiation in year 1: |
Phase III trial (CLARITY): Recovery of lymphocytes at the end of each treatment year: 86% [27] |
| Total lymphocyte counts: 42% | |||
| 2 months post-treatment initiation in year 2: | |||
| Total lymphocyte counts: 58% [27] | |||
| Dimethyl fumarate (Tecfidera®) |
1 Phase IIb and 3 Phase III trial (DEFINE, CONFIRM, ENDORSE): Grade 1: 9% Grade 2: 21% Grade 3: 7% Grade 4: < 1% [35] |
12 months post-treatment initiation: |
4 weeks: increased, but did not return to baseline [39] |
| Total lymphocyte counts: 30% [64] | |||
| Fingolimod (Gilenya®) | Grade 4: 18% [43] | Dose-dependent reduction: | 1–2 months [43] |
| Total lymphocytes: 70–80% [43] | |||
| Natalizumab (Tysabri®) | increases in peripheral lymphocytes [14] | 16 weeks [14] | |
| Ocrelizumab (Ocrevus®) |
RRMS: < LLN: 20.7% PPMS: < LLN: 26.3% Grades 1 and 2: majority Grade 3: 1% [58] |
2 weeks of treatment (first time point of assessment): | 2.5 years: 90% of patients had recovered CD19+ B cells (median: 72 weeks) [58] |
| Depletion of CD19+ B cells | |||
| No alterations in T cells [58] | |||
| Rituximab (MabThera®, Truxima®, Rixathon®) |
Phase II trial (OLYMPUS): 2 weeks of treatment: |
Phase II trial (OLYMPUS): 48 weeks: 35% of patients had recovered CD19+ B cells [59] |
|
| CD19+ B cells: 95% | |||
| No alterations in CD3+ T cells [59] | |||
| Siponimod (Mayzent®) |
Phase III trial (EXPAND): Grade 4: 1% [47] |
Dose-dependent reduction: | 10 days: 90% of patients [47] |
| Total lymphocytes: 70–80% [47] | |||
| Teriflunomide (Aubagio®) |
Phase III trials (TEMSO, TOWER, TENERE, TOPIC): Grade 1: 7.3% Grade 2: 2.2% No grade 3 or 4 lymphopenia was reported [62] |
6 weeks of treatment: |
Recovery from grade 1 lymphopenia: 10.6 weeks Recovery from grade 2 lymphopenia: 16.6 weeks [63] |
| Decrease in white blood cell count: 15% (mainly neutrophils and lymphocytes) [62] |