B35-46 Last Line, Significant Impact: Obinutuzumab in Refractory Granulomatosis With Polyangiitis (GPA)

Abstract Introduction We present a case of granulomatosis with polyangiitis (GPA) refractory to rituximab and cyclophosphamide that responded clinically and biochemically to obinutuzumab, an anti-CD20 monoclonal antibody used to treat follicular lymphoma and lymphocytic leukemia. Case description A 55-year-old man with a history of biopsy-proven GPA with pulmonary, upper airway, and cutaneous involvement, presented to the hospital with 1-week of dyspnea on exertion (DOE) and subjective fever, chills, and night sweats. At the time of presentation he was receiving cyclophosphamide due to prior rituximab failure, with his most recent infusion approximately 2 weeks prior to hospitalization. Labs were notable for leukocytosis to 13.7 and elevated inflammatory markers (ESR 90 mm/h, CRP 290 mg/L). Serum proteinase 3 (PR3) was elevated to 168 AU/mL, the highest level recorded for this patient, although ANCA indirect immunofluorescence assay was negative. CT chest demonstrated new multifocal consolidations and mediastinal lymphadenopathy. He was started on broad spectrum antimicrobials. Sputum cultures later returned positive for few MRSA. Rheumatology recommended 2 doses of IVIG until additional infectious workup was obtained to determine safety of glucocorticoids. He underwent a bronchoscopy with bronchoalveolar lavage (BAL). Examination of the left mainstem bronchus revealed ulceration. BAL showed 2,000 red blood cells and 651 white blood cells (78% neutrophils). Cultures from BAL specimens were negative. Transbronchial biopsies showed extensive necrosis, inflammatory infiltrates, and microabscesses with no bacterial or fungal organisms identified on stains, overall consistent with GPA flare. He completed 7 days of vancomycin for MRSA pneumonia and subsequently started pulse dose steroids that was transitioned to a prolonged prednisone taper. He was started on obinutuzumab prior to discharge, with later resolution in DOE and improvement in CRP to 15 mg/L. Repeat CT chest is currently pending. Discussion First line treatment of GPA is induction therapy with either rituximab, an anti-CD20 monoclonal antibody, or cyclophosphamide, an alkylating antineoplastic agent, in combination with glucocorticoids. Rituximab is often preferred due to its favorable safety profile and comparable efficacy. However, there are few guideline-based options for patients with refractory disease. Obinutuzumab is an anti-CD20 monoclonal antibody used to treat follicular lymphoma and lymphocytic leukemia. Existing data in refractory GPA is limited to case series and small retrospective studies, but available evidence suggests efficacy in achieving disease remission and B-cell depletion. This case highlights the importance of continued research on the effectiveness and potential side effects of obinutuzumab in treating refractory GPA. This abstract is funded by: None