AL amyloidosis is a plasma cell dyscrasia in which clonal immunoglobulin light chains misfold, forming fibrils that are deposited in tissues and vital organs. Immunomodulatory drugs including thalidomide, lenalidomide (LEN), and pomalidomide have activity in AL amyloidosis. We conducted a prospective phase II trial of LEN with dexamethasone (DEX) in the treatment of AL amyloidosis (ClinicalTrials.gov: NCT00091260), enrolling 82 patients from 2004–2011. We now report the final results of this trial. The majority of the patients were treated with LEN at a starting dose of 15 mg/d for 21 days out of a 28 day cycle, and received DEX at 20 or 40 mg weekly, depending upon age, congestive heart failure, and/or peripheral edema, and aspirin prophylaxis for venous thromboembolism (VTE) was used for most. Of the 82 patients, the median age was 62 (range, 40–84) and 63% were men. 95% of the patients had prior therapy for AL, often including high dose melphalan and autologous stem cell transplantation. The median number of cycles delivered was 11 (range, 1–69). Of the 68 evaluable patients, 16% achieved a complete hematologic response, 44% achieved a partial hematologic response, 9% achieved a minor hematologic response, and 29% had no response to treatment. The median time to best hematologic response was 6 months. Sixty-three patients had quantifiable organ involvement prior to treatment with LEN/DEX, and 44% of those patients had measurable organ response. Reasons for discontinuation of study drug were side effects (29%), non-response (39%) and complete response or completion of trial (15%). The most common side effects during treatment were fatigue (88%), anemia (67%), muscle cramps (66%), dizziness/lightheadedness (60%), respiratory tract infections (55%), increased creatinine (56%) and skin rash (48%). In conclusion, LEN administration achieved a 60% hematologic response rate (CR+PR) even in heavily pre-treated AL patients, when used at a starting dose of 15 mg/d with weekly dose-modified DEX, VTE prophylaxis, and appropriate management of side effects.
Off Label Use: Lenalidomide for AL amyloidosis. Sanchorawala:Millennium: Research Funding. Zeldis:Celgene: Employment. Seldin:Celgene: Research Funding.
Asterisk with author names denotes non-ASH members.