Bortezomib Containing Regimens Are Highly Effective for Systemic AL Amyloidosis: Experience from a Single Center

Introduction. The spectrum and severity of organ involvement, usually dictate early outcomes in AL amyloidosis. With the advent of novel therapies, higher rates of responses have been noted. The goal of therapy is the prompt, profound and prolonged suppression of the AL clone. Based on the above mentioned, we performed a retrospective review of the use of bortezomib containing regimens to assess the rapidity and quality of response.

Methods. Patients with documented AL amyloidosis treated with bortezomib-containing regimens were identified from our Institutional database. Trop-T and NT-proBNP values at baseline, 3, 6 and 12 months were recorded when available. Hematological Response, Cardiac response and OR were assessed according to the more recent validation of the criteria response.

Results 31 patients treated with bortezomib-containing regimens from January, 2009 to April, 2014 were identified. Clinical characteristics are seen in Table 1. Median Troponin-T was 78 ng/L and median NT-pro-BNP was 680 ng/L. According to the Mayo Clinic staging criteria (2004): 12 patients were Stage I, 10 Stage II and 6 Stage III. Fourteen-patients received CyBORD (45%) and 15 patients bortezomib and dexamethasone in different combinations (48%). (Table 2) Seven-patients were previously treated and the rest received bortezomib-containing regimens as upfront therapy. ASCT was used in 2 patients and melphalan and dexamethasone in 5 more cases. After a median of 6 cycles (2-22), a HR was seen in 30 cases (96%) including: Complete Response in 10 (32%), Very Good Partial Response in 18 (58%) and Partial Response in 2 (6.45%). At 6 weeks, 29 patients had already achieved ³PR. Organ Response at 6 months was documented in 26 cases (83%). With respect to cardiac response, a ³30% decrease of Troponin-T was seen in 8 of 9 evaluable patients while a decrease of NT-proBNP of ³30% was observed in 7 of 7 evaluable cases (NTproBNP>650ng/L) at a median of 6 months. Only one patient discontinued therapy due to toxicity. At the time of analysis, 4 patients have died and 6 have already progressed.

In conclusion, bortezomib is a safe and tolerated therapy for AL patients showing rapid HR and cardiac responses assessed by NT-proBNP and TnT. The use of bortezomib in cardiac advanced disease is feasible but should be carefully monitored and dose adjustement is often required.

**NT-pro Brain Type Natriuretic Peptide

*** BMPC: Bone marrow plasma cells

CyBORD: Cyclophosphamide, bortezomib and dexamethasone