The Italian Medicines Agency Prospective Registry of Bortezomib-Based Treatment in AL Amyloidosis

Background: There is no licensed therapy for light chain (AL) amyloidosis; however, bortezomib (B) is considered standard upfront treatment. Existing data on safety and efficacy of B in AL amyloidosis derive from clinical trials and retrospective series from few referral centers and only partly reflect real-world practice. In 2011, the Italian Medicines Agency (AIFA) started a program to grant access to upfront B to patients with AL amyloidosis. Treated patients had to be enrolled in an online registry and prospectively followed during therapy. We report the treatment experience in this real-world setting. Methods: AL amyloidosis diagnosis required tissue typing with mass spectrometry or immuno-electron microscopy. Patients samples could be sent to the Pavia specialized center for typing, but patients were not treated under the supervision of the referral center. Subjects with multiple myeloma were excluded. Variables were collected at baseline and hematologic and cardiac responses were assessed after 8 weeks (approximately 2 cycles) according to the International Society of Amyloidosis criteria. The cox proportional model has been adopted to assess the risk of treatment discontinuation according to the baseline characteristics. Results: A total of 754 patients were treated between May 2011 and October 2019 and 605 were included in the analysis. Most common reasons for exclusion were retrospective data collection (45%), and incomplete data set (31%). Median age was 67 years (range 26-89 years). 82% of patients had heart involvement. Cardiac stage was I in 18% of subjects, II in 45%, IIIa in 21%, and IIIb, in 16%. Sixty-seven percent of patients had renal involvement, and 13% and 14% had severe (glomerular filtration rate [eGFR] between 30 and 15 mL/min) and end-stage (eGFR 180 mg/L in 41% of cases. Bortezomib was administered with dexamethasone (D) alone in 41% of patients, with cyclophosphamide and D (CyBorD) in 44%, and with melphalan and D (BMDex) in 13% of subjects. Other combinations were used in 2% of patients. In the overall population, the initial dose of B was attenuated (