Abstract
This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenström macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis. A total of 40 patients (23 men, 17 women; 43-84 years old) with Waldenström 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. 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. Drug-related pneumonitis was noted on CT in 58% of Waldenström macroglobulinemia patients treated with mTOR inhibitor therapy. Most common findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns. The present study has demonstrated that drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy is highly frequent, occurring in 58% of patients with Waldenström macroglobulinemia. The radiographic patterns of pneumonitis demonstrated cryptogenic organizing pneumonia and nonspecific interstitial pneumonia patterns, with overlapping features in 30% of the patients. The present study describes an initial attempt of a radiographic pattern-based approach to drug-related pneumonitis in the era of molecular targeting therapy, with a cohort of patients with Waldenström macroglobulinemia receiving mTOR inhibitor therapy as a paradigm, which might contribute to further understanding and in-depth interpretation of lung toxicity during novel cancer therapy.
Highlights
Drug-related pneumonitis represents one of the major categories of drug toxicity in cancer patients receiving systemic therapy and can be caused by direct cytotoxic, oxidative, or immune-mediated injuries [1]
The radiographic patterns of pneumonitis demonstrated cryptogenic organizing pneumonia and nonspecific interstitial pneumonia patterns, with overlapping features in 30% of the patients.The present study describes an initial attempt of a radiographic patternbased approach to drug-related pneumonitis in the era of molecular targeting therapy, with a cohort of patients with Waldenstrom macroglobulinemia receiving mammalian target of rapamycin (mTOR) inhibitor therapy as a paradigm, which might contribute to further understanding and indepth interpretation of lung toxicity during novel cancer therapy
Six patients were treated in a phase II trial of single-agent everolimus in patients with relapsed/refractory Waldenstrom macroglobulinemia and received everolimus 10 mg orally daily [2].Thirty-four patients were treated in a phase I trial of everolimus combined with rituximab with or without bortezomib; 6 patients were treated with everolimus and rituximab and 28 patients with everolimus, rituximab, and bortezomib
Summary
Drug-related pneumonitis represents one of the major categories of drug toxicity in cancer patients receiving systemic therapy and can be caused by direct cytotoxic, oxidative, or immune-mediated injuries [1]. A spectrum of radiographic manifestations are noted in drugrelated pneumonitis, the lung’s response to injury is limited and commonly demonstrates several types of histopathologic manifestations with corresponding radiographic patterns [1]. These can be described according to the classification of interstitial pneumonias and related lung diseases. Drug-related pneumonitis was noted on CT in 58% of Waldenstrom macroglobulinemia patients treated with mTOR inhibitor therapy. Most common findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns.
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