Chronic Lymphocytic Leukemia
Minimal Residual Disease and Plasma Biomarkers in Chronic Lymphocytic Leukemia: Today and Tomorrow
Minimal residual disease (MRD) status in chronic lymphocytic leukemia (CLL) is a promising marker that may help fine-tune treatment and improve long-term outcomes. MRD assessments are now routinely incorporated into clinical trials but are not quite ready for use in routine clinical practice.
Professor and D.B. Lane Cancer Research Distinguished Professor
“We have not yet determined how to use MRD data in the standard day-to-day treatment of patients with CLL; however, I think that this will come with the data that we are generating in our current clinical trials.”
MRD is very important for our current efforts in clinical trials. We know that if we can eliminate all detectable disease and achieve an undetectable MRD status, patients with CLL will do much better long-term with respect to remaining in remission and having increased long-term survival. We are building MRD into all of our clinical trials right now because it gives us an earlier indication of how effective our newer treatments are by showing the depth of remission, which is an important indication of disease-free and overall survival.
Currently, MRD assessment is less important in terms of standard of care in community practice, and we are not yet recommending that patients with CLL be assessed for MRD routinely. We have not yet determined how to use MRD data in the standard day-to-day treatment of patients with CLL; however, I think that this will come with the data that we are generating in our current clinical trials. I predict that MRD will be an important test in the community setting within the next couple of years, but we are not quite there yet.
One of the issues is the standardization of testing for MRD. Historically, we have used 4-, 6-, or 8-color flow cytometry, but there are limits in terms of sensitivity with flow cytometry compared with the next-generation sequencing that has recently been cleared by the US Food and Drug Administration. The clonoSEQ Assay (Adaptive Biotechnologies) is available commercially, and it is 100-fold more sensitive than the flow cytometry–based assay, but we currently do not recommend it because we just do not have the data that support the use of MRD in standard community practice.
There is a lot of laboratory work on the horizon that is designed to identify new plasma biomarkers, and I am optimistic that we will have some identified in the near future. Potential plasma biomarker candidates include circulating tumor DNA, proteomics, and RNA sequencing, but these are quite investigational at this point.
Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760. doi:10.1182/blood-2017-09-806398
Hallek M. Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment. Am J Hematol. 2019;94(11):1266-1287. doi:10.1002/ajh.25595
International CLL-IPI Working Group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17(6):779-790. doi:10.1016/S1470-2045(16)30029-8