Clinical And Neurophysiological Spectrum Of Peripheral Neurotoxicity In Patients With CD30-Positive Malignancies, Treated With Brentuximab Vedotin. (P4.107)

OBJECTIVE To describe the clinical and neurophysiological spectrum of neurotoxic peripheral motor involvement in patients treated with Brentuximab Vedotin. BACKGROUND Brentuximab Vedotin is an antibody-drug conjugate composed by the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyllauristatin E. Brentuximab vedotin is effective as a single-agent therapy for the treatment of relapsed or refractory CD30-positive malignancies such as classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Peripheral sensory neuropathy, grade 1 or 2 in severity, seems to be one of the most frequent adverse events. Grade 3 motor neuropathy is believed to be present only in a minority of patients. Discontinuation of treatment may be followed by improvement of the neurologic symptoms, but complete regression of the neuropathy is not the rule. CASE REPORTS We studied 7 patients treated with Brentuximab Vedotin for HL who developed a sensory-motor neuropathy. The degree of motor involvement varied from mild hyposthenia prevalent in distal muscles of the limbs to severe upper limb diplegia, mimicking motor neuron disease. The sensory-motor conduction study show principally a reduction of sensory-motor conduction velocities, with SAP and cMAP amplitudes reduced. Some patients, however, developed severe reduction of the amplitudes of proximal cMAPs resembling motor conduction blocks. The needle EMG study showed acute denervation in weak muscles, with high amplitude, polyphasic MUPs producing a less-than-full interference pattern. The discontinuation of the treatment and repeated plasmapheresis have been followed in our patients by progressive improvement of muscle strength. CONCLUSIONS Peripheral nerve neurotoxicity is a well known event in patients treated with antimicrotubule drugs and motor involvement is also possible, with severe impact on patients’ quality of life. More studies are needed to assess the incidence of peripheral neurotoxicity, the clinical and neurophysiological pattern of the neuropathy, the rate of reversibility and the presence of risk factors for grade 3-4 neurotoxicity. Disclosure: Dr. Plasmati has nothing to disclose. Dr. Pastorelli has nothing to disclose. Dr. Salvi has received research support from the Fondazione Hilarescere.