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Daratumumab is a monoclonal antibody targeting CD38 and is widely used in the treatment of multiple myeloma. While generally well tolerated, pulmonary toxicity is a rare and under-recognised adverse effect. We present the case of an elderly woman with multiple myeloma on maintenance daratumumab therapy who developed subacute hypoxic respiratory failure. Imaging revealed new-onset diffuse bilateral ground-glass opacities. Bronchoscopy with lavage was non-diagnostic. Extensive infectious and rheumatologic workup was unrevealing. The patient improved significantly with corticosteroids and discontinuation of daratumumab, supporting a diagnosis of drug-induced pneumonitis. This case highlights the importance of considering monoclonal antibody-induced lung injury in the differential diagnosis of respiratory symptoms in patients receiving long-term CD38-directed therapy.