Adaptation of a multiple myeloma minimal residual disease multicolor flow cytometry assay for real‐world practice

Abstract

BackgroundAchieving minimal residual disease (MRD) negativity following treatment for multiple myeloma (MM) is associated with improved progression free and overall survival. In the UK, MRD assessments in MM are not incorporated into routine clinical use outside trials. Widely used in other haematological malignancies, there is a role for widening the availability of myeloma MRD assays to laboratories outside larger treating centers.MethodsWe set up and assessed concordance of a multicolor flow cytometry (MCF) assay for MM MRD in collaboration with a reference center including validity following delayed processing of samples using an optimized fixation step. We then conducted a real‐world snapshot of MRD results in a cohort of newly diagnosed transplant‐eligible patients treated with UK standard induction therapies at the time of analysis.Results43 MCF MRD samples run in parallel with a reference center showed high correlation and minimal bias. 24 samples were split and processed in duplicate both fixed and fresh, with strong correlation, minimal bias, and no change in plasma cell phenotype by flow markers confirming a 6‐day delay in processing did not affect assay performance. A real‐world snapshot found 17% (10/58) of patients were MRD‐negative post‐bortezomib‐based triplet induction therapy.ConclusionsWe successfully adopted a reference MCF MM MRD method which was stable for up to 6 days following sample collection potentially allowing broader access of this assay to smaller laboratories which would facilitate further investigation of the prognostic value and clinical utility of MRD assessments outside the trial setting in real‐world practice.

Issue highlights—May 2024

“…In the UK, in a 2022 MRD assessment, MM was not incorporated into routine clinical use outside of trials. A report was released (McMillan et al, 2023) about achieving minimal residual disease (MRD) negativity following treatment for multiple myeloma (MM) is associated with improved progression‐free and overall survival. They suggest a reference MCF MM MRD method, which was stable for up to 6 days following sample collection, allowing broader access by smaller laboratories to further investigate the predictive value and clinical utility of MRD assessments.…”

Issue highlights—July 2023

“…As the next article depicts, MRD measurement and its optimization plays a significant role not only in lymphoid but also in myeloid neoplasms. Since MRD analysis is not yet included in routine diagnostics in the United Kingdom, McMillan et al adapted and validated a multicolor flow cytometry (MCF) assay for multiple myeloma (MM) MRD, allowing widespread usage of this assay in smaller laboratories for real‐world practice (McMillan et al, 2022). Achieving MRD negativity in MM is crucial for improved patient outcomes.…”

Issue highlights—September 2023

“…The persistence of measurable residual disease (MRD) is a strong indicator for adverse outcomes in acute myeloid leukemia (AML) and has been shown to be a valid surrogate marker for disease-free survival and overall survival, irrespective of patients' age, AML subtype, sample type, time of MRD assessment and MRD detection method (Short et al, 2020). Other hematopoietic malignancies such as B-and plasma cell lineages also benefit from MRD diagnostic assays (Chen et al, 2023;Gao et al, 2023;McMillan et al, 2023;Zhou et al, 2023).…”

“…The persistence of measurable residual disease (MRD) is a strong indicator for adverse outcomes in acute myeloid leukemia (AML) and has been shown to be a valid surrogate marker for disease‐free survival and overall survival, irrespective of patients' age, AML subtype, sample type, time of MRD assessment and MRD detection method (Short et al, 2020). Other hematopoietic malignancies such as B‐ and plasma cell lineages also benefit from MRD diagnostic assays (Chen et al, 2023; Gao et al, 2023; McMillan et al, 2023; Zhou et al, 2023). In a study by Wang et al (2023) their experience working under CLSI HL62 guidelines and FDA IDE (investigational device exemption) approval in the validation of a 12‐color AML MRD flow cytometry MRD assay is shared, including the details of panel design, analysis and interpretation.…”