Measurable Residual Disease for Lymphoid Neoplasms by Molecular Methods (Pilot - Not Accredited)

Programme objective To assess a laboratory's ability to identify trackable clonal immunoglobulin (IG) gene rearrangements from a diagnostic sample and subsequently detect and quantify measurable residual disease (MRD) using next generation sequencing (NGS)-based molecular methods.

Clinical/scientific background Measurable residual disease testing is a well-established predictor of outcome following treatment across virtually all haematological malignancies. It has become an established surrogate endpoint in clinical trials for new compounds in lymphoid malignancies and is increasingly used to guide standard patient care. Unlike chronic myeloid leukaemia, lymphoid malignancies lack a single pathognomonic genetic marker consistent across all patients. Instead, immunoglobulin gene rearrangements offer an ideal patient-specific target: each neoplastic lymphoid cell harbours identically rearranged heavy and light chain IG genes generated through somatic V(D)J recombination, producing a unique clonal sequence. NGS-based approaches allow the sensitive identification and quantification of these clonal IG rearrangements, with reported limits of detection in the range of 10⁻⁴ to 10⁻⁷ (1-3), and applicability to approximately 90% of patients. Whilst EQA/PT programmes are established for allele-specific oligonucleotide (ASO)-PCR and multi-parameter flow cytometry (MPFC) approaches to MRD detection, EQA provision for NGS-based IG MRD quantification is not yet established. This programme addresses that gap. In addition to assessing qualitative and quantitative performance, the programme reviews reporting practice including nomenclature, bioinformatics software and version reporting, MRD units, and limit of detection/quantification (LoD/LoQ) definitions, with the aim of informing harmonisation across the field.

Suitability Participation in this EQA programme is open to laboratories employing NGS-based molecular methods for the identification and quantification of clonal IG gene rearrangements in a measurable residual disease setting.

All EQA programme communications, data entry, and reports will be conducted exclusively in the English language. Participants must ensure proficiency in English to fully engage in the programme.

The programme welcomes participation from:

• Clinical Healthcare Laboratories
• Academic and Research Institutions
• In Vitro Diagnostics (IVD) Manufacturers
• Pharmaceutical Companies

Sample type/distribution Four lyophilised cell-based samples are issued per round. One diagnostic sample is provided to facilitate the identification of a dominant clonal IG gene rearrangement sequence to be used as an MRD target. Standardly, three follow-up samples are then issued for detection and quantification of the target rearrangement(s): two MRD-positive samples at different MRD levels, and one MRD-negative sample. Two rounds are issued per annum. The trial schedule can be found here: https://www.ukneqasli.co.uk/eqa-pt-programmes/trial-schedules/

Trial duration Trials for this programme are live/open for a minimum of 6 weeks. Please note, trials issued/closing in August or December are extended by 1 week. An automated email is sent 2 days prior to trial closure to any participant that has not yet returned results.

Subcontracted areas Pre-issue and post-closure testing of samples for this programme is subcontracted, although the final decision about sample suitability lies with the EQA provider. No other activities in relation to this EQA programme are subcontracted.

Updates to the programme for current or upcoming year Improvements to the data entry form are planned prior to the next trial distribution to improve user experience.

To register for this programme, please click here.

References

Wierda WG, et al. Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations. Leukemia 2021;35:3059–3072.

Kumar S, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17:e328–e346.

Short NJ, et al. Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: a consensus of North American experts. Am J Hematol 2019;94:257–265.