Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

Abstract

Oral melphalan and dexamethasone (MDex) is a standard treatment for patients with AL amyloidosis who are not eligible for stem cell transplantation at many referral centers. However, following encouraging reports on the activity of bortezomib combined with alkylators and dexamethasone, these combinations are being moved to frontline therapy. We compared the outcome of 87 patients treated with bortezomib plus MDex (BMDex) with that of 87 controls treated with MDex. Patients and controls were matched for age, cardiac and renal function and free light chain burden. A higher rate of complete responses was observed with BMDex (42 vs 19%), but this did not result in a survival improvement in the overall population. However, a significant survival advantage for BMDex was observed in patients without severe (New York Heart Association class III or IV) heart failure and with N-terminal pro-natriuretic peptide type-B <8500 ng/l. Patients treated with full-dose dexamethasone had similar response rates and survival whether they received bortezomib or not. Intermediate-risk patients who are not fit enough to receive high-dose dexamethasone are likely to take the greatest advantage from the addition of bortezomib to MDex.

Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death

“…A case-control study did not find a difference in the death rate at 6 months between MDex and bortezomib in combination with MDex. 8 Cardiac toxicity in bortezomib-treated patients exists.…”

“…5 For patients ineligible for ASCT, melphalan in combination with dexamethasone (MDex) showed effective results. 6 Bortezomib added to the alkylator/ corticosteroid backbone has increased the rate of deep hematological responses, 7,8 and bortezomib-based regimens are the most used induction regimens. Immunomodulatory drugs (IMiDs) have been less effective and less well tolerated in AL patients compared with myeloma, [9][10][11] but remain an effective treatment option for some patients.…”

Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study

“…The therapeutic options have now been increased by the establishment of the melphalan-dexamethasone protocol, 5 by the introduction of proteasome inhibitors such as bortezomib 6,7 and immunomodulatory drugs such as lenalidomide, 8,9 and by their use in combination therapies. [10][11][12][13] However, HDM offers the prospect of long-term remission in AL. [14][15][16] Therefore, it remains a therapeutic option for carefully selected AL patients at specialized centers, 15 although controversy regarding its pros and cons persists.…”

Addition of Cyclophosphamide and Higher Doses of Dexamethasone Do Not Improve Outcomes of Patients With AL amyloidosis Treated With Bortezomib

“…10,23 However, these studies have compared bortezomib-with non-bortezomibcontaining regimens. The prospective study comparing BMDex with MDex also compares a bortezomib-containing with a nonbortezomib-containing regimen; thus, our study is quite different in this respect.…”