Diplopia in Extramedullary Multiple Myeloma: Clinical Features, Management, and Outcomes at a Tertiary Cancer Center.

BACKGROUND: Extramedullary multiple myeloma (EMM) involving the skull base and orbit is an uncommon cause of diplopia. Prior reports, including our earlier series of 7 patients, are limited to small case series. The aim of this study was to characterize the clinical features, lesion patterns, management, and outcomes of EMM-associated diplopia in a large single-center cohort. METHODS: We identified 250 patients with International Classification of Diseases, 10th Revision codes for multiple myeloma and diplopia who were evaluated at the MD Anderson Cancer Center between 2016 and 2025. Inclusion criteria required pathology or MRI confirmed EMM with associated binocular diplopia. We summarized demographics, myeloma characteristics, lesion sites, ophthalmologic findings, treatments, and diplopia outcomes following external-beam radiation therapy. Patients with complete resolution were compared with those with partial/no resolution using Fisher exact, χ2, and t test or Mann‑Whitney test as appropriate. Overall survival from the onset of diplopia was assessed using the Kaplan-Meier method. RESULTS: The mean age at diplopia onset was 63.6 ± 9.5 years; 51.9% of patients were female and 75.0% had relapsed or refractory disease. IgG was the most common isotype (57.7%) followed by kappa light chain (55.8%). The majority of patients were Revised International Staging System stage 2 or 3. MRI commonly revealed skull-base involvement in 63.5% and orbital involvement in 42.3% of patients. Among 34 patients who underwent ophthalmologic examination, 82.4% had cranial nerve palsy, most commonly with sixth nerve palsy (61.8%). Fifty-one patients received external-beam radiation (median 2,000 cGy in 8 fractions). Of these, 60.8% achieved complete resolution of diplopia and 11.8% partial resolution, typically within 2 months. No clinical, anatomic, or treatment variables were found to be associated with diplopia resolution. The median overall survival after diplopia onset was approximately 15 months. CONCLUSIONS: EMM-related diplopia is often indicative of skull-base or orbital involvement in patients with advanced myeloma. Although radiation frequently improves or resolves diplopia, survival following symptom onset remains limited (median 15 months), notably shorter than that observed in general relapsed/refractory myeloma. EMM-related diplopia serves as a high-risk clinical marker that necessitating urgent neuroimaging and multidisciplinary management.