CASE HISTORY/EXAMINATION
A 71-year-old woman with a diagnosis of chronic phase CML since 2000 received frontline treatment with imatinib and achieved major molecular remission for 14 years. Her treatment course was interrupted for two months in 2007 by pancreatitis and for one month in 2008 after she developed nitrofurantoin-induced non-specific interstitial lung disease. Her respiratory condition almost resolved itself after discontinuing the drug and six months of prednisone treatment, which required nocturnal administration of 2L/min of oxygen through a nasal cannula. In 2014, the patient’s disease progressed and was treated with dasatinib, followed by nilotinib. Both treatments were discontinued because of grade 3 gastrointestinal and dermatological side effects, respectively. In January 2015, the patient started bosutinib at a daily dose of 500 mg orally. The patient developed one-month symptoms of diarrhea, nausea, and vomiting that resolved themselves after the bosutinib dose was reduced to 400mg. She achieved complete hematological, cytogenetic remission and a major molecular response (MMR) (BCR-ABL1<0.1%) within the first year. While on MMR, she was admitted to the cancer center in August of 2019 with symptoms related to progressive dyspnea and dry cough, and her daily oxygen requirements were increased to 4L/min through a nasal cannula.
She denied any environmental or occupational exposures or other drugs except for pantoprazole for managing gastroesophageal reflux disease. The pulmonary function test at baseline revealed restrictive ventilatory defects and decreased diffusing capacity (Table 1). The echocardiogram was normal. Computed tomography (CT) of the chest showed non-specific chronic interstitial lung disease and new moderate bilateral pleural effusions with a small pericardial effusion (Figure 1). An autoimmune panel was negative. The bronchoalveolar lavage was negative for infection and with a bland count. The right diagnostic thoracentesis showed sterile exudate with 88% lymphocytes concerning drug reaction. Pleural fluid culture and cytology were negative. The bronchoscopy findings and CT scan findings raised the suspicion of bosutinib-induced interstitial lung disease and pleural effusion. The patient discontinued bosutinib in October 2019. In January of 2020, the patient noted significant improvement in her cough and dyspnea and was no longer requiring oxygen treatment. The chest CT scan in January 2020 showed almost complete resolution of pleural and pericardial effusions and decreased peribronchovascular ground-glass opacities (Figure 2). Repeat spirometry showed improved pulmonary function (Table 1) in February of 2020. The patient presented with hematological and molecular features of CML relapse, for which she initiated treatment with ponatinib. After two months of treatment, she has not reported significant side effects from the medication.