Severe Lenalidomide-Induced Hypersensitivity Pneumonitis

Abstract 4982

Lenalidomide is an immunomodulatory agent that stimulates T-cell activation, enhances natural killer cells and inhibits cytokines, as tumor necrosis factor-alpha. It is FDA-approved for use in both transfusion-dependent myelodysplastic syndrome, especially 5q deletion syndrome and refractory and relapsed multiple myeloma. The known side effects are myelosuppression, diarrhea/constipation, fever, fatigue, rash and thromboembolism, while pulmonary complications are rarely reported. We present a patient with myelodysplastic syndrome on lenalidomide with acute pulmonary toxicity.

A 63-year-old Caucasian man was diagnosed with low-intermediate risk myelodysplastic syndrome with 5q deletion after presenting with anemia and thrombocytopenia. He was started on lenalidomide at 21mg daily dose but after 5 days began to develop dyspnea on exertion, cough and fever. He was admitted for treatment of community acquired pneumonia. Physical examination revealed a middle aged man in respiratory distress. Oxygen saturation on room air was 86%. Chest examination revealed dry crackles. Heart sounds were regular without murmurs or gallops. Laboratory tests revealed hemoglobin of 8.6g/dl, normal white count at 10,000 and platelets of 7,000/uL. BNP and echocardiogram were normal and chest radiography was initially unremarkable.

He was started on antibiotics but developed respiratory failure requiring endotracheal intubation and mechanical ventilation. CT scan of the chest showed diffuse interstitial reticulonodular opacities most prominent at the apices with scattered ground glass attenuation. Cultures from blood, sputum, urine and stool and brochoalveolar lavage did not reveal an infectious source. Broad spectrum antibiotics and antifungals were withheld. Clinical and radiologic improvement was noted after withdrawal of lenalidomide and initiation of steroids.

He was persistently transfusion-dependent hence lenalidomide was reintroduced. Within 6 days of lenalidomide, respiratory symptoms recurred. He later improved after withdrawal of the offending drug.

Our myelodysplastic patient developed acute respiratory failure after lenalidomide introduction which improved with steroids and drug withdrawal. He had symptom recurrence after reintroduction of lenalidomide. The exposure history, clinical and radiological examination, positive challenge test with exclusion of other etiologies support the diagnosis of lenalidomide-induced hypersensitivity pneumonitis. This is the third reported case of lenalidomide-induced hypersensitivity pneumonitis and it is likely that this entity is underdiagnosed due to concurrent steroid use especially in myeloma patients. Clinicians should be aware of this potential complication in patients who present with fever, hypoxemia and diffuse pulmonary infiltrates unresponsive to broad spectrum antibiotics as this disease is reversible if diagnosed early.