Diffuse Alveolar Hemorrhage Secondary to Ibrutinib Therapy in a Patient With Refractory Mantle Cell Lymphoma

Ibrutinib is a Bruton tyrosine kinase inhibitor that is approved by the FDA for the treatment of mantle cell lymphoma and other hematological malignancies. Bruton tyrosine kinases promote platelet aggregation, and, therefore, bleeding is a common side effect of ibrutinib. At least half of patients taking ibrutinib experience a bleeding event, and up to 10% may experience major bleeding. Patient-specific factors that predict bleeding events remain unknown. This report describes a case of diffuse alveolar hemorrhage in a 67-year-old male taking ibrutinib for refractory mantle cell lymphoma. He was initially admitted to the hospital for recurrence of mantle cell lymphoma and evidence of tumor lysis syndrome, including acute kidney injury and hyperuricemia. He was taking aspirin prior to being hospitalized and was thrombocytopenic. A deep vein thrombosis was noted following admission, and the patient was started on enoxaparin. Two days after starting ibrutinib as an inpatient, the patient developed diffuse alveolar hemorrhage, which was ultimately fatal. Bronchoscopy with bronchoalveolar lavage ruled out infectious and other etiologies. To our knowledge, this is the first case of diffuse alveolar hemorrhage associated with ibrutinib. Based on the available literature, it is unclear if the patient's recent aspirin use, concurrent enoxaparin, or thrombocytopenia was contributory. Further studies are necessary to clarify these patient-specific risks.

Keywords: adverse event; bruton tyrosine kinase inhibitor; diffuse alveolar hemorrhage; hematology; ibrutinib; mantle cell lymphoma; non-hodgkin lymphoma; oncology; pulmonology.