Anti-CD20 treatment has been associated with both lymphopenia and hypogammaglobulinemia, which can increase the risk of infection. Who develops lymphopenia and hypogammaglobulinemia and the time course is not well understood.
To evaluate risk factors in developing lymphopenia and hypogammaglobulinemia in anti-CD20 treated patients with multiple sclerosis (MS).
A random sample of patients with neuroimmune conditions treated with rituximab at the Rocky Mountain MS Center at the University of Colorado were identified and followed retrospectively. Patients who switched to ocrelizumab remained in the study. Patient characteristics, IgG, IgM, and absolute lymphocyte counts on rituximab/ocrelizumab were analyzed.
Laboratory data on 546 patients were studied including 527 MS and 17 neuromyelitis optica spectrum disorder patients with mean disease duration of 9.2 years, mean age of 44.1, 68.7% women and 76.5% Caucasians. Patients were followed for a mean of 30.2 months with a mean cumulative rituximab dose of 3,312mg. Of the 527 MS patients, 96 (17.6%) switched to ocrelizumab (mean cumulative ocrelizumab dose of 1,175mg). Fifty-seven (10.4%) patients had lymphopenia (≤500cells/mm3), 38 (7.4%) low IgG (≤500 mg/dL), and 143 (37.9%) low IgM (≤40 mg/dL). A decrease of 31.5mg/dl per year in IgG from 920mg/dL in year 1 to 857mg/dL in year 3 was observed. Respectively, median time to lymphopenia, low IgG, and low IgM were 11.3, 36.2 and 23.6 months. Of patients who developed low IgG (≤500 mg/dL), 73.9% had a preceding (34.8%) or concurrent initial low IgM (39.1%). Higher doses (per gram) of anti-CD20 increased the odds of low IgG (OR: 1.28, 95% CI: 1.12-1.47; p<0.001) and low IgM (OR: 1.31, 95% CI: 1.18-1.45; p<0.001), but not of lymphopenia (p=0.246). Similarly, follow-up time (months) on anti-CD20 therapy increased the odds of low IgG (OR: 1.49, 95% CI: 1.23-1.80; p<0.001) and low IgM (OR: 1.45, 95% CI: 1.28-1.65; p<0.001), but not of lymphopenia (p=0.237). Increasing age was associated with an increased odds of lymphopenia (OR: 1.03, 95% CI: 1.00-1.05; p=0.030), but not low IgG (p=0.27) or IgM (p=0.18). Males had greater odds of low IgM values compared to females (OR: 2.87, 95% CI: 1.84-4.48; p<0.001).
MS patients treated with anti-CD20 therapies frequently develop low IgM. Lymphopenia and low IgG are less common but should be monitored given their association with an increased risk of infections.