Ixazomib Plus Cyclophosphamide and Dexamethasone for Newly Diagnosed AL Amyloidosis

A regimen of ixazomib, cyclophosphamide, and dexamethasone produced hematologic responses in 57% of patients with previously untreated light-chain (AL) amyloidosis, according to data presented at the 2020 American Society of Hematology Annual Meeting & Exposition.

Ixazomib is the first approved oral proteasome inhibitor and is effective in combination with cyclophosphamide and dexamethasone (Cy-Dex) for treating multiple myeloma. Bortezomib, an intravenous or subcutaneous proteasome inhibitor, has shown previous efficacy in the treatment of newly diagnosed AL amyloidosis and is commonly used in combination with Cy-Dex. In this phase II trial, investigators evaluated the efficacy of an all-oral regimen of ixazomib plus Cy-Dex for patients with untreated AL amyloidosis.

Thirty-five patients with newly diagnosed biopsy-proven AL amyloidosis with organ involvement were enrolled. Patients with severe organ involvement were excluded. Cardiac involvement was seen in 23 patients (65.7%), renal involvement in 19 (54.3%), and nervous system involvement in five (14.3%). Over a 28-day cycle, patients received ixazomib 4 mg orally on days one, eight, and 15, as well as cyclophosphamide 500 mg and dexamethasone 40 mg weekly for 12 cycles. After completion, ixazomib maintenance was continued until disease progression. The primary endpoint was hematologic response rate.

At data cutoff, eight patients remained in the study, with a median follow up of 4.4 months. The overall hematologic response rate was 57%, with a complete response in five patients (14%), a very-good partial response in nine (26%), and a partial response in six (17%). Five cases of confirmed organ response have been observed so far, with two cases each of cardiac and renal and one case of hepatic involvement. Median progression-free and overall survival have not yet been reached. Hematological progression was observed in four patients, and six patients have died. Seventeen patients have left the study for institution of alternate therapy. Grade 3 or higher adverse events (AEs) were observed in 41% of patients.

“The all-oral regimen of ixazomib, cyclophosphamide, and dexamethasone is active in patients with previously untreated AL amyloidosis with hematologic responses observed in 57% of patients, including complete responses. Organ response has been observed but will likely need longer follow-up for accurate assessment, given the delay in organ responses in this disease. Further evaluation of this combination is warranted,” the researchers concluded.