Recurrent late-onset neutropenia after ofatumumab treatment in a case of multiple sclerosis

OBJECTIVE: Immunomodulatory treatment options for multiple sclerosis show an inverse risk‒benefit ratio of side effects and treatment efficacy. Although rare, anti-B-cell therapies can cause acute or late-onset neutropenia. METHODS: We report a case of severe recurrent fluctuating neutropenia after ofatumumab treatment. RESULTS: We observed four recurrences even after pausing with ofatumumab and repeated granulocyte stimulating factor (G-CSF) treatment. In total, neutropenia occurred five times and was associated with recurrent pulmonary, urinary tract, and skin infections. Bone marrow investigation revealed no signs of lymphoma or leukemia. Interestingly, routine molecular testing revealed two gene variants of unknown significance for BCORL1 and ASXL1, both of which play a role in hematopoiesis. The neutrophil count recovered spontaneously six months after the cessation of treatment with ofatumumab. DISCUSSION: This case highlights the necessity of identifying patients at risk and monitoring white blood cell counts regularly for up to 6 months after initial neutropenia.