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 Updated on: Jan 9 2014

Minimal Residual Disease (MRD): monitoring and clinical impact

 

Subject
In actual clinical practice many young patients achieve complete remission (CR). Despite this all patients eventually relapse as a consequence of residual disease. In order to develop effective maintenance strategies prolonging time to disease progression, it may be important to monitor MRD levels by simple and fast techniques which however, need standardisation, optimisation and evaluation for analysis of MRD as (i) a prognostic parameter and (ii) as tool for early detection of disease progression.


Present Status
Current approaches to assess tumour load are based on morphological assessment of bone marrow biopsies and electrophoresis to detect changes in the serum and urine paraprotein levels. However, sensitivity is limited, and in actual clinical practice even patients achieving a stringently defined complete remission (CR) eventually relapse as a consequence of MRD. New and more sensitive approaches to measure MRD are based on flow cytometry (FC) and PCR. Numerous strategies – rarely comparable between studies -have been applied. In theory, MRD monitoring may provide the very strongest prognostic information, which could be the basis for a risk-adapted therapy of MM, and in practice it is the fastest way to evaluate potential responses to therapy and to detect relapse early. However, its actual prognostic value still has to be elucidated.


Preview Programme Proposal
We will evaluate the role of residual disease monitoring to determine prognosis, to stratify patients for “tailored therapy” and as a surrogate end point for to assess efficacy of new drugs An essential preliminary step of this approach is the harmonization of the laboratory practices throughout Europe. The following plan is proposed;

  • assess targets (immunoglobulin heavy chain [IgH] rearrangements, light chain rearrangements, k deleting element rearrangements, partial rearrangements and chromosome 14 translocations) and strategies (consensus-PCR, allele specific [ASO] PCR) for MRD detection by PCR
  • assess panels of antibodies and procedures for MRD detection by FC including new multiparameter approaches
  • define a standardized protocol for MRD monitoring, including time points of sample collection (diagnosis, before therapy cycles, follow-up), to be used in a multicenter setting
  • define putative prognostic threshold levels of MRD, and evaluate the predictive value of results of MRD analyses regarding survival in comparison to conventional prognostic parameters, FISH-results and monitoring by serum and BM biopsies in prospective trials
  • discuss and define the use of MRD as a surrogate end point in the evaluation of new drugs
  • develop external quality control programmes


Deliverables and Cooperations

  • database with SOP for MRD detection techniques
  • a unified method for MRD monitoring to be applied in future clinical trials performed by EMN
  • to develop a database of genetic maps, primers and protocols for clonality detection and residual disease detection
  • to establish a quality control programme to ensure consistency across the network
  • to implement standard approaches for flow cytometric detection of residual disease


Beyond 18 months the primary goal is validate the impact of MRD in clinical practice and document its efficacy in redefinition of CR, PR, NR and PD.

 

Contact
Dr.med. Wolfgang Willenbacher
Innere Medizin
Abt. Hämatologie-Onkologie
Leiter Studienambulanz & HAEM-Labor
Projekt Manager LACCITO
Universitaetsklinik Innsbruck
Anichstr.35
A-6020 Innsbruck

Phone: 0043(0)512-504-82057
Fax: 0043(0)512-504-25448
E-mail:
Wolfgang.Willenbacher@uki.at

Secr. Hans E. Johnsen | Depart. of Haematology | Aalborg University Hospital | Sdr. Skovvej 15 | DK-9000 Aalborg | Denmark | T:+45 9766 3871 | F:+45 9766 6369