Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) for the treatment of AL amyloidosis: Experience at a single Institution

Abstract

Introduction: AL amyloidosis is a clonal, non-proliferative plasma cell disorder characterized by the presence of light chain deposits among different tissues. Recently, bortezomib, has been reported to successfully induce hematological and cardiac responses for patients with AL amyloidosis. In addition, bortezomib has been combined with cyclophosphamide and dexamethasone (CyBorD), showing a high degree of hematological response. Based on the above mentioned, we aimed to assess the role of CyBorD in the treatment of patients with AL amyloidosis at our Institution. Methods: 40 consecutive patients have been treated with bortezomib-containing regimens at our center from 01/2010 to 01/2015. Among these cases, 22 (55%) have received CyBorD. Cyclophosphamide was given at 300 mg/m2 (PO) once weekly, dexamethasone 20-40 mg (PO) once weekly and Bortezomib 1.3 mg/m2 (IV or SQ) once weekly 3 out of 4 weeks in a 28-day cycle. The primary objective of the study was to assess rapidity of hematological and cardiac response. Results: Clinical characteristics are shown in Table 1. Median age at diagnosis was 63 years and 14 patients were male (63%). Three-cases have received prior therapies, ASCT in 1 and melphalan and dexamethasone in 2 patients. At the time of analysis, 19 patients are still alive and 3 patients have already progressed at a median follow-up of 11 months. A HR was seen in 19 out of 22 patients (ORR, 86%) after a median of 4 cycles (range, 1-19). CR (n1⁄46) and VGPR (n1⁄47) were seen in 13 cases (59%). Interestingly, partial response (n1⁄46, 27%) or better was seen after a median of 6 weeks in the responder cases. Organ response has been achieved in 59% of cases. Cardiac response based on high sensitive-troponin-T was seen in 6/10 cases (60%) and 7/11 (63%) based on NT-proBNP at a median of 12 and 6 months, respectively. CyBorD was well-tolerated and only one patient discontinued therapy due to autonomic neuropathy. No cases with cardiac involvement exhibited major decompensated CHF (congestive heart failure). In conclusion, CyBorD is an efficacious regimen for patients with AL Amyloidosis, providing with a high degree of organ and hematological responses. The impact of CyBorD on advanced heart dysfunction cases remains unclear but it seems that these patients still require a different approach maintaining a dismal prognosis.