Minimal Residual Disease

Minimal residual disease (MRD) provides an indication of tumour burden after treatment and is predictive of relapse, shorter progression free survival (PFS) and OS for most therapies. It can also be used to track disease activity as well as treatment response (Hallek, 2017; Sun & Weistner 2015). In the CLL8 trial, MRD levels below 1 CLL cell in 10,000 leukocytes (i.e. <10-4) correlated with longer PFS and this was more pronounced in the FCR (fludarabine plus cyclophosphamide and rituximab) treatment arm (Bottcher et al., 2012; Hallek et al., 2010).

In a recent analysis of two Phase III trials (the CLL8 trial, fludarabine plus cyclophosphamide [FC] with or without rituximab [R] and the CLL10 trial, FCR vs. bendamustine and rituximab [BR] by the GCLLSG) MRD negativity was seen in 82% of patients with a complete response (CR) and 48% of patients with a partial response (PR). PFS was significantly different between patients with a CR who were MRD negative (MRD-) and MRD positive (MRD+) (61 m vs. 35 m), and between patients with a PR and MRD- and those with CR and MRD+ (54 m vs. 35 m). PFS for MRD- CR and MRD- PR groups were not significantly different. The data indicate that patients with a CR or PR had much better prognosis if they had MRD (Kovacs et al., 2019).