Pb2151: clinical features and outcomes of diffuse pulmonary light chain amyloidosis: a rare presentation of systemic al amyloidosis

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Systemic light chain (AL) amyloidosis can involve lungs in 3 different ways: nodular, tracheobronchial, or diffuse. While the natural history of localized amyloid deposition in the form of nodular or tracheobronchial deposits is well-described in literature, the clinical characteristics and outcome of systemic AL amyloidosis with diffuse alveolar-septal or lung parenchymal involvement is not well-defined. Aims: The aim of our study was to define the baseline characteristics, natural history, and outcome of patients with systemic AL amyloidosis that presented with predominantly diffuse pulmonary involvement. Methods: The prospectively maintained databases of Columbia University Irving Medical Center (NY, USA) and University of Pavia (Pavia, Italy) were searched for consecutive cases with diffuse pulmonary AL. Diagnosis was made by lung biopsy in all except 1 case, where diagnosis was made based on clinical signs & symptoms along with imaging. Results: A total of 13 patients with diffuse pulmonary AL were identified. The median age at diagnosis was 68 years (range, 49-87), with 5/13 patients (39%) being male, and 10/13 (77%) with lambda light chain involvement. The median time interval from initial symptoms to diagnosis was 11 months (range, 6-63). The most common presenting symptom was progressive exertional dyspnea (n=8). Other presenting features were pneumonia, pleural effusion, hemoptysis, and pulmonary nodules on imaging. On computed tomographic (CT) scan of chest at diagnosis, 7/13 patients demonstrated multiple nodules (associated with other findings including 3 with ground-glass opacities, 1 with parenchymal consolidation, 1 with interstitial fibrosis, 1 with cysts, and 1 with diffuse micronodules alone). The baseline characteristics are shown in Table 1. The most common frontline treatment regimen was Melphalan-Dexamethasone (n=5; 39%), followed by Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone (Dara-VCD; n=2; 15.4%). The remaining patients received Cyclophosphamide-Lenalidomide-Dexamethasone (n=2), Cyclophosphamide-Thalidomide-Dexamethasone (n=1), VCD (n=1), Dara-CD (n=1), and high-dose dexamethasone (n=1). Among patients with diffuse pulmonary AL receiving bortezomib-based regimens, the starting dose of bortezomib was 0.7 mg/m2 in 2 patients and 1.3 mg/m2 in 1 patient. Only one patient had received auto-transplant, and subsequently received a single lung transplantation (right), which was successful with symptomatic improvement and the patient was alive at most recent follow-up 2.5 years from lung transplant. Hematologic very good partial response or better (≥VGPR) was achieved in 5/13 patients (39%). A total of 8/13 patients were alive at latest follow-up, with the median follow-up of surviving patients being 34 months (range, 3-93). The median overall survival (OS) is not reached (95% CI, 6.7 months-NR), and 1-year estimated OS was 75.2% (95% CI, 44.8-91.9). Among 5 patients who had available data on follow-up CT chest, only one patient, who had also achieved a rapid hematologic complete response (at 1 month from treatment initiation) demonstrated significant improvement in consolidative changes on right lung. Summary/Conclusion: We report the natural history of a large cohort of patients with diffuse pulmonary AL amyloidosis. Notably, approximately 1/3rd of patients with diffuse pulmonary AL present with lung as the only vital organ involved, which highlights the importance of a strong index of suspicion in patients with monoclonal gammopathy and characteristic signs and symptoms. We also provide the proof-of-principle that lung transplantation is feasible in patients with diffuse pulmonary AL.Keywords: Autologous bone marrow transplant, Amyloidosis, AL amyloidosis