LIGHTNING STRIKES TWICE? ALVEOLAR HEMORRHAGE AND SINUS NODE DYSFUNCTION REQUIRING PACEMAKER AFTER INITIATING BORTEZOMIB FOR MULTIPLE MYELOMA

Abstract

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease 3 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma. Neuropathy, constipation, and edema are common side effects. Cardiotoxicity causing dysrhythmia and pacemaker placement have occurred, yet controversy exists regarding the risk of adverse cardiac events based on recent data. To date only 18 cases of alveolar hemorrhage (AH) associated with bortezomib have been described; symptoms occur after a median of four doses and respond to glucocorticoids. CASE PRESENTATION: DB is an 82 year old previously healthy male who presented with fatigue and arm pain admitted for a pathologic humerus fracture, acute renal failure and anemia. Bone marrow biopsy (48% k-restricted plasma cells via morphology, IgA K/L ratio of 345) confirmed the diagnosis of multiple myeloma. The patient received dexamethasone and 2.6mg of bortezomib on D1 and D4. Lenalidomide was held due to NSAID-induced nephropathy. The patient initially experienced distal neuropathy and extremity edema but was discharged and scheduled for outpatient therapy. At home, DB had a syncopal episode secondary to orthostasis and was admitted to the hospital where he received his third dose of bortezomib on D8 per protocol. A chest film ordered for worsening cough revealed right lower lobe infiltrates and bilateral pleural effusions. DB then developed sinus node dysfunction with multiple syncopal episodes requiring a pacemaker. On D26, he developed worsening hypoxia with increased effusions and ground glass opacities on CT imaging. He had preserved ejection fraction and normal IVC collapsibility on echocardiogram. Cefepime, vancomycin, sulfamethoxazole-trimethoprim, and prednisone yielded no improvements. Fat pad biopsy was negative for amyloid. Bronchial lavage was not done due to concern for inability to extubate post-procedure. Worsening renal function precluded CTA for pulmonary embolism. On D33 he was intubated due to respiratory failure. A BAL revealed three progressively bloody aliquots suggestive of AH and the patient was treated with 1g IV solumedrol for three days. Repeat BAL on D39 revealed markedly less bloody aliquots, suggestive of improvement and he was extubated on D48. DISCUSSION: Similar to previously cases, we demonstrate AH after three doses of bortezomib, bilateral infiltrates and effusions, lavage-proven hemorrhage and response to steroids. Unlike others, our case appears to be the first Caucasian male and the oldest known patient to experience this toxicity. Our case has an additional complexity of sinus node dysfunction after induction of bortezomib suggesting an even more rare potential toxicity of bortezomib. CONCLUSIONS: This may represent the first case of concomitant AH and sinus node dysfunction associated with bortezomib and highlights the importance of early recognition and rapid initiation of high dose glucocorticoid therapy. Reference #1: Sugita, Y., et al (2018). Early-Onset Severe Diffuse Alveolar Hemorrhage after Bortezomib Administration Suggestive of Pulmonary Involvement of Myeloma Cells. Reference #2: Diwadkar, Sachin, et al. “Bortezomib-Induced Complete Heart Block and Myocardial Scar: The Potential Role of Cardiac Biomarkers in Monitoring Cardiotoxicity.” Case Reports in Cardiology, vol. 2016, 2016, pp. 1–5., https://doi.org/10.1155/2016/3456287. Reference #3: Laubach, Jacob P., et al. “A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma.” British Journal of Haematology, vol. 178, no. 4, Mar. 2017, pp. 547–560., https://doi.org/10.1111/bjh.14708. DISCLOSURES: No relevant relationships by Patrick Bagley, source=Web Response No relevant relationships by Alexander Dew, source=Web Response