Autologous stem cell transplantation (ASCT) is an important treatment modality in light chain (AL) amyloidosis. Use of reduced-dose melphalan conditioning is common, given the associated organ and functional decline. The impact of full-intensity melphalan conditioning (n=314) was compared to reduced-dose conditioning (n=143). Patients in the full-intensity group were younger, with better performance status, fewer involved organs, lower tumor burden and lower Mayo stage. Full-dose conditioning was associated with higher rate of very good partial response or better (79% vs 62%; P<0.001), complete response rate (53% vs 37%; P=0.003) and organ response rate (74% vs 59%; P=0.002) as compared to reduced-dose conditioning. PFS was superior in the full-intensity group compared to the reduced-dose group (4-year PFS 55% vs 31%; P<0.001) as well as a longer overall survival (OS) 4-year OS (86% vs 54%; P<0.001). In addition, the OS and PFS were significantly lower in the reduced-dose group compared to the full-intensity group in Mayo stage III/IV as well as stage I/II. A multivariate analysis confirmed an independent impact for conditioning dose on PFS/OS. This study calls for re-assessment of the use of reduced-dose conditioning in ASCT for AL amyloidosis.
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NT, EM, MAG and SKK designed the study, collected the data, analyzed the data, wrote the first draft and approved the final version of the manuscript; SS, AD, MQL, DD, FKB, SRH, WJH, WG, RW, TVK, NL and PK provided patient management, critically reviewed the first draft and approved the final version of the manuscript; and RC provided critical review and approved the final version of the manuscript.
Angela Dispenzieri: Celgene Corp. (research funding), Millennium Pharmaceuticals Inc. (research funding), Pfizer Inc. (travel grant) and Janssen Pharmaceuticals Inc. (research funding), MQL: Celgene Corp. (research funding), DD: Karyopharm Therapeutics (research funding), Amgen Inc. (research funding), Millenium Pharmaceuticals (Research funding). PK: Millennium Pharmaceuticals Inc. (Takeda Pharmaceutical Co. Limited; research funding), Celgene Corp. (research funding) and Onyx Pharmaceuticals Inc. (Amgen Inc.; research funding). MAG: Celgene Corp. (Honoraria), Millennium Pharmaceuticals Inc. (Consultancy and Honoraria), Onyx Pharmaceuticals Inc. (Honoraria), Novartis (Honoraria), Smith Kline (Honoraria), Prothena (Honoraria), Ionis (Honoraria), Amgen Inc. (Honoraria). SKK: Celgene Corp. (consultancy and research funding), Millennium Pharmaceuticals Inc. (consultancy and research funding), Novartis (research funding), Onyx Pharmaceuticals Inc. (consultancy and research funding), AbbVie (research funding), Janssen (consultancy and research funding), BMS (consultancy and research funding). The remaining authors declare no conflict of interest.
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