Carfilzomib-Induced Pneumotoxicity in a Lung Transplant Recipient

Abstract

Introduction Development of de novo donor-specific antibodies (DSA) in lung transplant (LTx) recipients is a risk factor for antibody-mediated rejection (AMR). There is no consensus on treatment protocols for patients who develop de novo DSA, but strategies include plasmapheresis (PLEX), intravenous immunoglobulin (IVIG), and carfilzomib (CFZ), a second-generation proteasome inhibitor. Dyspnea is common in patients with multiple myeloma treated with CFZ; however, lung injury in LTx recipients has not been reported. We report a case of CFZ-related pneumotoxicity in a bilateral LTx recipient undergoing treatment for possible AMR. Case Report A 71-year-old bilateral LTx recipient (October 2011) with moderate mitral regurgitation was diagnosed with probable AMR in June 2018, characterized by de novo DSA (DQ7, MFI 20,634) and FEV1 decline, but no radiographic changes or capillaritis. He was treated with PLEX, IVIG, and rituximab and had monthly PLEX/IVIG until January 2020. He tolerated the treatment well and his FEV1 stabilized. After a 5-month moratorium of PLEX/IVIG, the patient's MFI increased from 4,337 in November 2019 to 15,444 in June 2020; however, FEV1 remained stable. PLEX was resumed and CFZ was administered in August 2020, which led to a hypertensive emergency, hypoxemic respiratory failure requiring mechanical ventilation, renal failure requiring continuous renal replacement therapy, and corticosteroid therapy for persistent hypoxemia and radiographic infiltrates despite a negative fluid balance. He was extubated, his renal function recovered, and he was discharged home on supplemental oxygen and a corticosteroid taper. On outpatient follow-up, he had a 600-ml drop in FEV1, complained of severe dyspnea on exertion with hypoxemia, appeared euvolemic on physical exam, and was readmitted with evidence of ongoing lung injury. Radiographic infiltrates and hypoxemia improved with additional steroid therapy. Summary A bilateral LTx recipient presented with hypoxemic respiratory failure immediately after a 5-day course of PLEX and an infusion of CFZ. Although volume overload was a factor, persistent lung injury despite aggressive diuresis and blood pressure control suggests CFZ pneumotoxicity. Although the mechanism of CFZ lung injury is not understood, it appears to be steroid responsive, both in our patient and in other cases of proteasome inhibitor-induced pneumotoxicity.