Management and Resolution of Hypersensitivity Pneumonitis-Related Events in Japanese Patients Treated with Amikacin Liposome Inhalation Suspension in the CONVERT and INS-312 Clinical Trials.

In the phase 3 CONVERT trial, amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) achieved greater culture conversion than GBT alone in the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD). In the original analysis of safety data in CONVERT, the rate of hypersensitivity pneumonitis, a prespecified group of adverse events of special interest, was higher in patients receiving ALIS plus GBT (3.1%; n = 7) versus GBT alone (0.9%; n = 1), with half of the cases reported in Japanese patients. We present a summary of serious adverse events of hypersensitivity pneumonitis that investigators deemed related to ALIS treatment in Japanese patients enrolled in CONVERT (n = 3) and its extension study (INS-312; n = 1). Patients were women older than 65 years diagnosed with pneumonitis (n = 3) or interstitial lung disease (n = 1) after initiation of ALIS (range 3-189 days). Following ALIS discontinuation and medical intervention, all four patients recovered from pneumonitis. Additional investigator-collected imaging and serum Krebs von den Lungen 6 (KL-6) data were available for two of these patients, permitting assessment of KL-6 and the potential diagnostic role of radiographic findings. At the time of diagnosis, one patient had ground-glass opacity, and the other patient had consolidation in the right lower lobe of the lung; both patients had serum KL-6 levels > 600 U/mL. Changes in chest radiography and KL-6 levels at the onset of respiratory symptoms during ALIS treatment suggest that these assessments may help guide management strategies for potential hypersensitivity pneumonitis in patients taking ALIS.Clinical Trial Registration: NCT02344004 (CONVERT) and NCT02628600 (INS-312).