Abstract
This case report describes the successful use of ofatumumab, a fully humanized anti-CD20 monoclonal antibody, in a 62 years old male with monoclonal gammopathy of undetermined significance (MGUS) associated chronic inflammatory demyelinating polyneuropathy. The patient presented with acute limb weakness, glove-like paresthesia, and respiratory involvement, alongside elevated anti-ganglioside antibodies (anti-GM4 IgM and IgG) and λ-type IgM-M proteinemia. Despite initial therapies including intravenous immunoglobulin, efgartigimod, and immunosuppressants, he experienced recurrent relapses. Treatment with ofatumumab combined with methylprednisolone resulted in complete peripheral CD19+ B cell depletion, improved nerve conduction velocities, and sustained clinical remission. The findings highlight the efficacy of ofatumumab in targeting pathogenic CD20+ B cell clones, thereby disrupting autoantibody production implicated in immune mediated peripheral nerve injury. This case underscores the potential of B cell directed therapy for refractory MGUS associated neuropathies, offering a novel approach when conventional immunotherapies fail. Further multicenter studies are warranted to establish standardized protocols and optimize long term outcomes through combination regimens targeting both B cell and plasma cell compartments.