Minimal Residual Disease as a Possible Predictive Factor for Relapse in Patients With AL Amyloidosis

Study Summary

This protocol will assess patients with AL amyloidosis who achieve a complete response (CR) or very good partial response (VGPR) to therapy for minimal residual disease (MRD). Three approaches to MRD testing will be used since there is no established method. The investigators will clone and sequence each patient's light chain (LC) gene and design patient-specific primers to evaluate genomic DNA from future marrow specimens. Whole genome sequencing (WGS) will be used to test baseline and follow-up marrow cell DNA, seeking copy number variations in chromosomes 1 and 2 or 22, and structural variations in chromosomes 11 and 14, consistent with the known genetic abnormalities in AL and with clonal LC gene use. Plasma protein analysis by mass spectrometry will also be used to look for fragmentary protein sequences associated with the culprit LC gene of each subject. The feasibility and predictive value of these three approaches in patients achieving CR or VGPR will be evaluated. This protocol will help provide insight into the ways that the disease changes and progresses. MRD testing is likely an important next step in AL management.

Primary Outcome

After achievement of a CR or VGPR, minimal residual disease testing (using Q-PCR, WGS, and plasma protein analysis by mass spectrometry) will be done annually for up to 3 years. These tests will show either the presence of absence of minimal residual disease. These findings will then be correlated with progression free survival as assessed through standard clinical tests for AL amyloidosis.

Conditions Studied

Study Locations (1)