Carfilzomib-induced life-threatening lung injury in refractory multiple myeloma

Carfilzomib is a second-generation selective proteasome inhibitor that is commonly used in the treatment of relapsed or refractory multiple myeloma. Carfilzomib is associated with respiratory side effects, such as cough, dyspnea, and upper respiratory tract infection. However, severe pulmonary toxicity is rare and is only reported in a few case reports.

Here, we present a case of a 65-year-old male with refractory multiple myeloma who developed a life-threatening lung injury during his third cycle of carfilzomib. The patient presented with a decreased level of consciousness and was found to have Type I respiratory failure. He was admitted to the intensive care unit, where he was intubated. Blood cultures and viral panel were negative. The patient received a prolonged course of antibiotics with 2 days of hydrocortisone.

After discharge, repeated myeloma workup showed disease progression and carfilzomib was reintroduced. The next day, he presented with fever, vomiting, and hypoxia. Chest x-ray showed congestive lung changes with patchy airspace opacities. Repeated echocardiography showed normal ejection fraction with moderate pulmonary hypertension (RVSP 46 mm Hg). The patient was transferred again to the ICU and kept on continuous positive airway pressure. Antibiotics were started, and blood cultures and respiratory viral panels were negative for any infectious organism. The patient improved in terms of inflammatory markers and oxygen requirements. Treatment with carfilzomib was stopped permanently.

Pulmonary toxicity associated with carfilzomib in patients with multiple myeloma can be potentially life-threatening. The mechanism with which carfilzomib induces lung-related AEs is still not fully understood. In our patient, carfilzomib-induced lung injury was evident after rechallenging the patient with carfilzomib, in the radiographic x-ray changes and the new onset moderate pulmonary hypertension. Healthcare providers should be encouraged to report rare adverse events in order to identify the risk factors that can predispose patients to the development of these adverse events.