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.