Survival impact of achieving minimal residual negativity by multi-parametric flow cytometry in AL amyloidosis

Abstract

Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected or not. Among patients who achieved deep response (i.e. very good partial response or complete response) to first-line therapy, lack of clonal marrow plasma cells as measured by MFC was associated with improved progression-free survival (PFS) compared to patients with residual clonal plasma cells (3-year PFS 88% vs. 46%, p = .003), particularly among patients who achieved a complete response (3-year PFS 100% vs. 33%, p = .001). Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p = .02) and higher frequency of renal response (100% vs. 68%; p = .005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.

Keywords:

• Flow cytometry
• response
• survival
• minimal residual disease
• light chain

Disclosure statement

Eli Muchtar reports no disclosure. Angela Dispenzierireceived research funding from Celgene, Millennium, Pfizer, and Janssen and travel grant from Pfizer. Dragan Jevremovic reportsno disclosure. David Dingli received research funding from Karyopharm Therapeutics, Amgen, and Millenium Pharmaceuticals. Francis Buadi reports no disclosure. Martha Q. Lacy received research funding from Celgene. Wilson Gonsalves, Rahma Warsame, Taxiarchis Kourelis and Suzanne R. Hayman report no disclosure. Prashant Kapoor received research funding from Takeda, Celgene, and Amgen. Nelson Leung, Stephen Russel, John A. Lust, Yi Lin, Ronald S. Go, Steven Zeldenrust, Robert A. Kyle and Vincent Rajkumar report no disclosure. Shaji Kumar received consultancy from Celgene, Millennium, Onyx, Janssen, and BMS and research funding from Celgene, Millennium, Novartis, Onyx AbbVie, Janssen, and BMS. Morie A. Gertz received consultancy from Milleniu and honoraria from Celgene, Millenium, Onyx, Novartis, Smith Kline, Prothena, Ionis.