Acute respiratory distress syndrome after exposure to carfilzomib (KYPROLIS)

ABSTRACT

Case Report Introduction Plasma cell leukemia is very rare and an aggressive form of leukemia with a poor prognosis. Interim analysis of a phase II trial (EMN12/HOVON 129) using carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with PCL ≤65 years showed a very good partial response or greater response in 80% with 33% achieving at least a complete response. Carfilzomib (Kyprolis TM) is a proteosome inhibitor and is associated with ARDS and acute respiratory failure in 2% of the cases per FDA package insert. We present a case report of acute respiratory distress syndrome presumed to be potentiated 2/2 to carfilzomib infusion. Case A 58-year-old male with a history of hypertension, recent COVID-19 infection and new diagnosis of untreated Plasma Cell Leukemia presented to our hospital with worsening chest pain, fatigue and dyspnea. Vitals on admission were notable for BP 158/88, HR 101, Tmax 99F and sating 100% on room air. Peripheral blood exam showed WBC 27.7 x109/L, Hb 8 gm/dl, platelet 121000, corrected calcium 13.3 mg/dl, creatinine 1.16 mg/dl, total protein11 g/ dl, uric acid 8.2 mg/dl, B-2 micro globulin 5.8 mg/L, Mspike 5.6 g/dl;IgA lambda type. CT Chest abdomen pelvis revealed diffuse lytic bone lesions. Due to inability to obtain bone marrow biopsy from limited resources after Hurricane Ida and aggressive nature of the cancer, treatment was initiated based off a previous flow cytometry from the peripheral blood which showed 55% plasma cells. Patient started on chemotherapy with Cyclophosphamide, Carfilzomib, and dexamethasone with plans to change to Revlimid from cycle 2. He was also started on fluid hydration and Zometa for hypercalcemia. Patient also received aggressive blood pressure control with metoprolol, amlodipine and IV labetalol as needed. After 2nd dose of Kyprolis, he developed acute hypoxic respiratory distress and was initiated on Bipap. Chest Xray was concerning for fluid overload and/or evolving pneumonia. He was supported with diuretics and broad-spectrum antibiotics;however, he eventually was intubated. He was also started on high dose steroids. Repeat CT chest was negative for thrombosis, but showed extensive bilateral pleural -parenchymal opacities. He had a bronchoalveolar lavage with no obvious infection. Over the next 2 days, patient showed improvement and eventually self-extubated. After his recovery, we continued chemotherapy with Kyprolis and he has tolerated it without issues. Discussion The etiology of ARDS is likely multifactorial, however Kyprolis may have played a major role in his decompensation mainly due to the timing and known side effects of the medication. Based on a study from 2018, only 5 case reports of Kyprolis-associated non-infectious progressive lung injury were found at that time. Clinicians should be mindful of Kyprolis induced lung injury and emphasize the need for tight blood pressure control and careful administration of intravenous fluids to decrease the possibility of lung injury.