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14-02-2012 | Immunology | Article

Combination regimen effective in AL amyloidosis

Abstract

Journal

MedWire News: Treatment with a combination of bortezomib, cyclophosphamide, and dexamethasone (CyBorD) produces rapid hematologic responses in patients with amyloid light-chain (AL) amyloidosis, according to two publications forthcoming in Blood.

AL amyloidosis is a rare disease in which immunoglobulin light chains come together to form damaging amyloid deposits in organs such as the kidneys, heart, liver, and intestines.

The condition shares some characteristics with multiple myeloma (MM), and has typically been treated, with limited success, with alkylator-based chemotherapy.

CyBorD is a relatively new treatment regimen that has produced "rapid and profound" responses against MM. Because of its success in MM, Joseph Mikhael and colleagues from the Mayo Clinic in Scottsdale, Arizona, USA, and Christopher Venner and his team from University College London Medical School in the UK, investigated the efficacy of CyBorD in patients with AL amyloidosis.

Mikhael and co-workers performed a retrospective analysis of 17 patients with confirmed and symptomatic AL amyloidosis. Ten (58%) had symptomatic cardiac involvement and 14 (82%) had two or more organs involved.

The patients all received two to six cycles of bortezomib (1.5 mg/m2 weekly), cyclophosphamide (300 mg/m2 orally weekly), and dexamethasone (40 mg weekly). The treatment was given prior to autologous stem cell transplantation, or as an alternative to standard high-dose therapy for those deemed ineligible, or as salvage therapy for those with failed prior therapy.

The researchers report that 16 of the 17 patients had a hematologic response to treatment after a median time of 2 months. Twelve (71%) achieved complete response (CR; normalization of the light chain ratio with no monoclonal protein by immunofixation) and four (24%) patients achieved a partial response (PR; 50% reduction in M-spike or absolute light chain level).

At 21 months of follow up, nine (75%) of the 12 patients who achieved a CR remained in CR status, with a median response duration of 22 months.

In the second study, Venner and team reviewed data for 43 patients who received a slightly different CyBorD regimen up front or at relapse: bortezomib (2.0 mg/m2 weekly), cyclophosphamide (350 mg/m2 orally weekly), and dexamethasone (40 mg weekly), for up to eight 2-weekly cycles.

The overall response rate in this group was 81.4%, with 39.5% achieving CR and 41.9% achieving PR. The researchers note that a significantly higher CR rate was seen in patients treated upfront versus those treated at relapse (65.0 vs 21.7%). The time to maximal response was 4.1 months.

Both groups of researchers conclude that the CyBorD is a highly effective combination for the treatment of AL amyloidosis, and warrants further investigation in prospective randomized trials.

Mikael and team add that the high response rate they observed "is significant, especially in light of other studies that show that hematological response is associated with long-term survival."

By Laura Cowen

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