[goldmine848]

Minimal residual disease (MRD) testing

by goldmine848 on Sat Jul 19, 2014 7:23 pm

Picking up on the discussion in response the Beacon Staff's posting of the results on the response to RVD followed by transplant, I am curious about the emphasis on the development of a standardized testing protocol for MRD negative status.

If I am correct that MRD testing is done on bone marrow samples taken from a bone marrow biopsy, is it not subject to the same weakness as all testing based bone marrow samples: the disease is patchy and can absent from some areas of the body and present elsewhere?

[Cheryl G]

Re: Minimal residual disease (MRD) testing

by Cheryl G on Sat Jul 19, 2014 7:50 pm

Hi Andrew,

I think that, with current MRD sensitivities, the short answer to your question is yes. You run the risk of a patient registering as MRD negative even though a marrow sample from somewhere else in the body might register MRD positive. I don't know, though, if this issue will go away in the longer term as MRD testing technology becomes more and more sensitive.

One approach that is attempting to get around the patchy marrow problem is to do MRD testing using blood samples. This article discusses results of a study looking into the technology:

Vij R et al, "Deep sequencing reveals myeloma cells in peripheral blood in majority of multiple myeloma patients", Clin Lymphoma Myeloma Leuk. 2014 Apr;14(2):131-139.e1. Epub 2013 Oct

Abstract

INTRODUCTION: The evaluation of myeloma cells in multiple myeloma (multiple myeloma) patients has generally been limited to the assessment of bone marrow involvement because of the sensitivity limitations of traditional minimal-residual-disease-detection methods.

MATERIALS AND METHODS: We developed a sequencing-based method to identify myeloma cells in bone marrow (BM) and peripheral blood (PB) samples, based on their unique immunoglobulin gene rearrangements, that can detect cancer clones at levels well below 1 in 1 million leukocytes (0.0001%). In this multisite study, we used this sequencing method to determine the fraction of patients with myeloma cells in their PB at diagnosis and posttreatment time points.

RESULTS: Using this sequencing approach, we detected myeloma cells in the PB in the vast majority of multiple myeloma patients (44/46, 96%). We demonstrated a clear correlation (R(2) = 0.57) between myeloma clone levels in paired BM and PB samples, and noted that PB clone levels were approximately 100-fold lower than levels in BM samples. The sequencing assay demonstrated a clear sensitivity advantage in the BM compartment and at least equivalent sensitivity in the PB compared with that of monoclonal-protein results.

CONCLUSION: This study highlights the promise of a blood-based, sequencing minimal-residual-disease assay that can be used to measure multiple myeloma disease burden at different time points and various disease stages.

http://www.sciencedirect.com/science/article/pii/S2152265013004345

[Ron Harvot]

Re: Minimal residual disease (MRD) testing

by Ron Harvot on Sun Jul 20, 2014 10:13 am

I have had only one bone marrow biopsy and that was done at the time of diagnosis back in Feb of 2009. My myeloma is tracked primarily using the sFLC [serum free light chain] assay. I know I have residual disease as the SPEP shows a faint IgG Kappa marker, even though I generally do not have an M spike. (I have had M spike as high as 0.2 g/dL, which may disappear with the next test.) I was initially diagnosed with IgG Kappa light chain multiple myeloma.

The MRD testing is a relatively recent development and not common in the clinical setting. I am not sure how it fits, if at all, with respect to the decisions on ongoing treatment. For example, it may or may not be a factor in determining if an individual should receive maintenance treatment after the initial induction and/or transplant. Assuming that maintenance is recommended, I don't believe that MRD is sophisticated enough to help determine what form of treatment should follow.

Therefore, there is value in determining whether a person has had a very deep response to initial treatment, but how that translates into future treatment recommendations is blurry.

Ron