RISK-ADAPTED INTRAVENOUS MELPHALAN WITH ADJUVANT THALIDOMIDE AND DEXAMETHASONE FOR NEWLY DIAGNOSED UNTREATED PATIENTS WITH SYSTEMIC AL AMYLOIDOSIS: INTERIM REPORT OF A PHASE II TRIAL

摘要

From previous clinical trials employing intravenous (iv) melphalan and mobilized stem cell support for patients with systemic AL amyloidosis we have learned that survival depends on the number of major viscera involved with amyloid, on the degree of cardiac involvement, and on the response of the plasma cell disease to melphalan (1-3). We have also learned that adjusting the dose of melphalan modulates toxicities and that prompt treatment with intravenous melphalan is appropriate, as opposed to several cycles of oral therapy as a prelude to transplant (4, 5). Therefore, this clinical trial builds on those results and seeks to answer two questions: does risk-adapted melphalan dosing reduce treatment-related mortality and does adjuvant therapy for persistent disease after SCT enhance the response of the plasma cell disease?Eligible patients have systemic AL with symptomatic visceral involvement, are within 12 months of diagnosis and untreated. Transthyretin and fibrinogen A-alpha genes are sequenced to rule out hereditary amyloid (6, 7). Based on risk assignment, patients receive 100, 140 or 200mg/m2 with stem cell support (low-risk) or two cycles of 40mg/m2 (high-risk) (8). Patients with persistent plasma cell disease at 3 months receive adjuvant therapy with either thalidomide and dexamethasone or dexamethasone alone. Primary endpoints are survival, and organ system and hematologic responses. We report interim results.