Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy: Radiographic Pattern-Based Approach in Waldenstrom Macroglobulinemia as a Paradigm

Background. This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenstrom macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis. Materials and Methods. A total of 40 patients (23 men, 17 women; 43-84 years old) with Waldenstrom macroglobulinemia treated in 2 trials of the mTOR inhibitor everolimus were retrospectively studied. Chest computed tomography (CT) scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by the consensus of three radiologists, evaluating the extent, distributions, and specific findings. The radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia. Results. Drug-related pneumonitis was noted in 23 patients (58%). The median time from the initiation of therapy to the onset of pneumonitis was 5.7 months. Lower lungs were involved in all 23 patients, with a higher extent than in the other zones (p<.001). The distribution was peripheral and lower in 11 patients (48%) and mixed and multifocal in 10 (44%). The findings were bilateral in 20 patients (87%). Ground glass opacities (GGOs) and reticular opacities were present in all 23 patients, with consolidation in 12, traction bronchiectasis in 2, and centrilobular nodularity in 1. The pattern of pneumonitis was classified as cryptogenic organizing pneumonia (COP) in 16 (70%) and nonspecific interstitial pneumonia (NSIP) in 7 (30%), with overlapping features of COP and NSIP in 7 patients. Conclusion. Drug-related pneumonitis was noted on CT in 58% of Waldenstrom macroglobulinemia patients treated with mTOR inhibitor therapy. Mostcommon findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns.