[New Onset of Graves' Orbitopathy Following Bendamustine-Rituximab (BR) therapy in a Patient with Chronic Lymphocytic Leukemia: A Case Report and Literature Review].

Graves' orbitopathy (GO) is a progressive autoimmune disorder of visual organ, mostly associated with Graves' disease (GD). Although rituximab has been used as an off-label therapy for steroid-resistant GO, paradoxical immune reactivation has also been reported. We present a rare case of GO that developed after bendamustine-rituximab (BR) therapy for chronic lymphocytic leukemia (CLL). A 73-year-old male with a 3-year history of GD, presented with new onset of bilateral proptosis, diplopia, and decreased visual acuity, that happened two weeks after his second BR cycle for CLL. The anamnesis was negative for both smoking, and radioiodine therapy. Laboratory studies showed persistently elevated thyrotropin receptor antibodies levels in plasma, and extraocular muscle enlargement on orbital MRI. The active phase (CAS 6/6) of moderate-to-severe (EUGOGO) GO was diagnosed. Despite two courses of intravenous methylprednisolone (cumulative dose - 12.2 g) and 10 retrobulbar dexamethasone injections, the patient progressed to dysthyroid optic neuropathy. Although the patient had a predisposing autoimmune background, the close temporal association with BR therapy, progressive disease course, and glucocorticoid resistance suggest that chemotherapy-induced immune dysregulation played a critical role in triggering GO. Rituximab-related B-cell depletion and cytokine release syndrome may have facilitated T-cell-mediated orbital inflammation, while bendamustine-induced lymphopenia further disrupted immune tolerance. This case illustrates the potential for paradoxical autoimmune activation following BR therapy in a predisposed patient. Clinicians should monitor for GO signs, and symptoms before, during, and after BR therapy in patients with underlying thyroid autoimmunity. Further clinical trials are needed to verify this phenomenon.