Contributions
Abstract: P1217
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Rituximab (RTX) is a chimeric recombinant anti-CD20 monoclonal antibody (mAb) primarily targeting B cell populations, resulting in depletion of CD20-expressing B cells. Ocrelizumab is a fully humanized anti-CD20 mAb that interacts with a slightly different epitope, with enhanced B cell cytotoxicity. Previous clinical trials have reported minimal impact of these agents on immunoglobulin (Ig) G levels, and a mild-to-moderate impact on IgM levels, although hypogammaglobulinemia has been documented under other settings. We evaluated the impact of RTX therapy on Igs in a real-world cohort that had transitioned primarily from natalizumab (NTZ) to RTX for treatment of multiple sclerosis (MS).
Methods: A retrospective review was undertaken of all patients receiving RTX for treatment of MS at a single US center. 29 patients were identified, of which 69% had transitioned from natalizumab therapy due to high risk of progressive multifocal leukoencephalopathy (PML). RTX exposures ranged from 1-4 courses. Serum Ig levels were measured prior to each course, and the lowest value observed after treatment initiation was compared to pre-treatment level.
Results: The proportion of patients with IgM below the lower limit of normal (LLN; 55 mg/dL) increased from 25% to 71% with RTX treatment (p < 0.001). Mean IgM levels decreased from 79.5 to 50.6 mg/dL (p < 0.001). The proportion of patients with IgG below the LLN (565 mg/dL) increased from 3% to 24% with RTX treatment (p < 0.001). Mean IgG decreased from 905.0 to 778.3 mg/dL (p = 0.014). RTX treatment did not increase the proportion of patients (7%) with IgA below LLN (70 mg/dL), but did induce a 13.2% decrease in mean levels (175.1 vs 152.1 mg/dL; p < 0.001).
Conclusions: These results suggest that reductions in Ig levels may occur at higher rates in a real-world setting than observed in clinical trials of B cell depleting agents. Prior exposure to NTZ was exclusionary for those trials, and the effect of NTZ on Ig levels is unknown. PML risk is increased in primary hypogammaglobulinemia patients and with anti-CD20 therapy, occurring primarily with concomitant immunosuppressant use. Further evaluation of chronic hypogammaglobulinemia secondary to anti-CD20 therapy as a risk factor for PML is warranted, especially in high risk populations.
Disclosure:
Madeline Foley: nothing to disclose
Ryan Metzger: nothing to disclose
Abstract: P1217
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Rituximab (RTX) is a chimeric recombinant anti-CD20 monoclonal antibody (mAb) primarily targeting B cell populations, resulting in depletion of CD20-expressing B cells. Ocrelizumab is a fully humanized anti-CD20 mAb that interacts with a slightly different epitope, with enhanced B cell cytotoxicity. Previous clinical trials have reported minimal impact of these agents on immunoglobulin (Ig) G levels, and a mild-to-moderate impact on IgM levels, although hypogammaglobulinemia has been documented under other settings. We evaluated the impact of RTX therapy on Igs in a real-world cohort that had transitioned primarily from natalizumab (NTZ) to RTX for treatment of multiple sclerosis (MS).
Methods: A retrospective review was undertaken of all patients receiving RTX for treatment of MS at a single US center. 29 patients were identified, of which 69% had transitioned from natalizumab therapy due to high risk of progressive multifocal leukoencephalopathy (PML). RTX exposures ranged from 1-4 courses. Serum Ig levels were measured prior to each course, and the lowest value observed after treatment initiation was compared to pre-treatment level.
Results: The proportion of patients with IgM below the lower limit of normal (LLN; 55 mg/dL) increased from 25% to 71% with RTX treatment (p < 0.001). Mean IgM levels decreased from 79.5 to 50.6 mg/dL (p < 0.001). The proportion of patients with IgG below the LLN (565 mg/dL) increased from 3% to 24% with RTX treatment (p < 0.001). Mean IgG decreased from 905.0 to 778.3 mg/dL (p = 0.014). RTX treatment did not increase the proportion of patients (7%) with IgA below LLN (70 mg/dL), but did induce a 13.2% decrease in mean levels (175.1 vs 152.1 mg/dL; p < 0.001).
Conclusions: These results suggest that reductions in Ig levels may occur at higher rates in a real-world setting than observed in clinical trials of B cell depleting agents. Prior exposure to NTZ was exclusionary for those trials, and the effect of NTZ on Ig levels is unknown. PML risk is increased in primary hypogammaglobulinemia patients and with anti-CD20 therapy, occurring primarily with concomitant immunosuppressant use. Further evaluation of chronic hypogammaglobulinemia secondary to anti-CD20 therapy as a risk factor for PML is warranted, especially in high risk populations.
Disclosure:
Madeline Foley: nothing to disclose
Ryan Metzger: nothing to disclose