Abstract:

The treatment of AL amyloidosis aims to eradicate the plasma cell clone and eliminate toxic free light chain production. Only in a minority of patients the plasma cell clone is completely eradicated; residual light chain production may still exist while clonal relapse may occur. We used sensitive next-generation flow cytometry (NGF) to detect minimal residual disease (MRD) in AL amyloidosis patients at complete haematologic response. MRD evaluation was feasible in 51 of 52 (98{%}) tested patients and at a median sensitivity of 2.3 × 10−6 MRD was undetectable in 23 (45{%}). An organ response occurred in 86{%} of MRDneg vs 77{%} in MRDpos; renal response in 15/17(88{%}) of MRDneg vs in 14/16(87.5{%}) of MRDpos and cardiac response in 10/10(100{%}) of MRDneg vs 11/15(73{%}) of MRDpos patients. After a median follow-up of 24 months post MRD testing, no MRDneg patient had a haematologic relapse vs 6/28(21{%}) MRDpos (p =.029). Pooling haematologic and organ progressions, 9 (32{%}) MRDpos patients had disease progression vs only 1 (4{%}) MRDneg patient (p =.026). In conclusion, MRD detection using NGF has profound clinical implications, so that AL patients with undetectable MRD have a very high probability of organ response and a very low probability of haematologic relapse.

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