Tough case and I would tend to agree with the comments from Brian. Although findings of BOS etc have been reported with nilotinib and imatinib for that matter, I am intrigued as to why it is limited to a single lobe. I would tend to favor that this is a transplant related side effect and most likely due to changes secondary to an infectious process in that lobe which has not been identified. Was there any history of an aspiration pneumonia in the past? In fact the infection may now be successfully treated and what is being seen are secondary changes to that infection. I would tend to favor an atypical mycobacterial infection. I am not sure that what is seen is due to the TKI therapy or that switching therapy will change things. I am not even sure that discontinuing TKI therapy completely, although there are good reasons as noted by Brian for considering stopping, will change things. Stepping out very far on a limb here, I would wonder if stopping the TKI might result in a flare in the inflammatory process and worsen what is going on. It is unfortunate that the area cannot be resected. Were any of the transbronchial biopsies actually sent for bacterial culture or just pathology.

There are rare reports of pulmonary toxicity with nilotinib and it is also possible that this is a complication of the patient’s allogeneic stem cell transplant. Known late complications include, idiopathic pneumonia syndrome (IPS), bronchiolitis obliterans syndrome (BOS), and cryptogenic organizing pneumonia (COP). Since his PCR has been undetectable for nine years, one possibility would be to discontinue nilotinib with close observation of his PCR for BCR-ABL and the pulmonary process. It would also be possible to switch to bosutinib, but with close monitoring for recurrence of pulmonary hypertension, if the patient or physician do not want to risk relapse.

The patient born 1966 was in May 2005 he was diagnosed to have CML CP and imatinib was started. In Dec 2005 he developed an extramedullary blast crisis paravertebrally Th 6-7 followed by overt lymphatic blast crisis. He was treated with two cytostatic regimens and radiotherapy against the tumour. In May 2006 an allogeneic stem cell transplantation was performed. In Aug 2006 he developed a recurrent blast crisis. Dasatinib donor lymphocyte infusions (x3) were started. He has had undetectable BCR-ABL transcript since Jan 2007.

During dasatinib he developed bilateral pleural effusions, and was treated with pleurodesis, with a thoracotomy and pleurectomy and installation of talcum powder in the right side. Dasatinib was changed to nilotinib in 2009 after development of pulmonary hypertension. The current dose of nilotinib is 300+150mg /day.

Since 2014 the patient has developed an expanding infiltrate with dense consolidations and caverns in the right upper lobe, now extending to the entire upper lobe. Repeated bronchoscopies have not shown any malignant cells or infection. Transbronchial biopsy has shown chronic inflammation and peribronchial fibrosis. The lesion has not been considered to be resectable.

Could nilotinib have caused or contributed to this development? Change to bosutinib?