Efficacy of the combination of bortezomib and dexamethasone in systemic AL amyloidosis

Abstract

Bortezomib -Dexamethasone (Btz/Dex) is an active regimen in patients with multiple myeloma and has been used in few patients with amyloidosis. Here we report a retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients with AL amyloidosis. 18 patients (69%) received Btz/Dex as first-line treatment. Organs most frequently involved were kidneys (100%) and heart (35%), 5 patients (19%) had > 2 organs involved. The overall response rate was 54% (14 of 26 patients), with 8 patients (31%) achieving a hematologic complete remission (CR). All patients who reached a CR received Btz/Dex as first-line therapy. Median time to response was 7.5 weeks. Improvement in organ function was noticed in 3 patients (12%). Median progression free survival (PFS) and overall survival (OS) was 5.0 and 18.7 months, respectively; in CR patients, however, median PFS and OS have not yet been reached. Toxicities were manageable, with haematological side effects being most common. No grade 3/4 neuropathy was observed. Our results confirm the activity of bortezomib/dexamethasone in patients with AL amyloidosis and suggest that patients achieving a CR have a marked benefit for survival.

Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival

“…20 A significantly higher CR rate was seen in patients treated upfront versus those at relapse (65.0% vs 21.7%; P ϭ .003). This appears superior to other studies in upfront-treated patients (for bortezomib and dexamethasone, RR ϭ 81% and CR ϭ 47%; for CTD, RR ϭ 70% and CR ϭ 27%) 11,21 or even autologous stem cell transplant, and is similar to previously documented experience with bortezomib-alkylator combinations (RR ϭ 90% and CR ϭ 62%). 3 In responding patients, the time to maximal response was 4.1 months (4.1 months upfront vs 4.2 months at relapse; P ϭ .95).…”

“…This compares favorably with the 1-year PFS of 72.2%-74.6% seen in the recent phase prospective 1/2 trial of bortezomib. 4 Consistent with data published previously, 1,11,18,20,21,23 attaining a CR was correlated with a significant improvement in median PFS (not reached for patients in CR vs 17.5 months for those not in CR; 95% confidence interval, 8.5-26.5; P ϭ .002; Figure 1A) and for a VGPR-dFLC (not reached for VGPR-dFLC vs 9.1 months for non-VGPR patients; 95% CI, 6.0-12.2; P ϭ .026; Figure 1B). There was no significant difference in the median PFS between those attaining a CR and those with a VGPR-dFLC but not a CR (P ϭ .22), but small numbers and the retrospective nature of the study limit interpretation.…”

“…Initial retrospective series using bortezomib with and without steroids 1,7,11 documented response rates (RRs) between 72% and 80%. Recent phase 1 and phase 1/2 trials have corroborated this prospectively, demonstrating an overall RR of 50%-68.8% and complete response (CR) rates of 20%-37.5%, respectively.…”

“…[1][2][3][4][5][6][7][8] Although the efficacy of proteosome inhibitors is based several different mechanisms, of particular relevance to AL amyloidosis is "proteostasis" because of both the excess light-chain production and accumulation of the misfolded proteins. 9,10 Based on the success of bortezomib in myeloma treatment regimens, initial retrospective series showing efficacy with bortezomib with or without dexamethasone 1,7,11 in AL amyloidosis have laid the groundwork for recent prospective clinical trials showing high response rates but have also raised questions about response durability. 4,5 Given the excellent outcomes in myeloma using a steroid/ alkylator backbone in combination with bortezomib, 12,13 similar strategies have been explored in AL amyloidosis.…”

Light chain amyloidosis 2012: a new era

“…In this study, SAE were observed in 29% of cases, most common being fluid retention and hypotension, and TRM was 3% (Kastritis et al, 2010). A smaller series of patients (n = 26) was reported from a multicentre retrospective analysis outside the context of a clinical trial (Lamm et al, 2011) and showed similar results of 54% response and 31% CR with the use of BDex. In most clinical trials, patients with severe cardiac involvement are excluded.…”