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Summary of the 2019 Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling.

ABSTRACT: The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup has organized an annual workshop focused on minimal residual disease (MRD) testing and immune profiling (IP) in multiple myeloma since 2016. In 2019, the workshop took place as an American Society of Hematology (ASH) Friday Scientific Workshop titled "Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma." This workshop focused on 4 main topics: the molecular and immunologic evolution of plasma cell disorders, development of new laboratory- and imaging-based MRD assessment approaches, chimeric antigen receptor T cell therapy research, and statistical and regulatory issues associated with novel clinical endpoints. In this report, we provide a summary of the workshop and discuss future directions.

SUBMITTER: Holstein SA

PROVIDER: S-EPMC7529908 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Summary of the Third Annual Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling.

Project description:The third annual Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling was held on November 29, 2018, at the American Society of Hematology (ASH) annual meeting. This workshop featured the latest research focused on minimal residual disease (MRD) assessment and immune profiling (IP) in myeloma as well as discussion of the statistical and regulatory issues intrinsic to the development of MRD as a surrogate endpoint. In this report, we provide a summary of the workshop and focus on the integration of MRD and IP assessment into trial design and clinical practice.

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Summary of the Second Annual BMT CTN Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling.

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BMT CTN Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling: Summary and Recommendations from the Organizing Committee.

Project description:The Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling was convened on December 1, 2016 at the American Society of Hematology meeting to discuss the emerging data and technologies for minimal residual disease assessment and immune profiling in myeloma. Particular emphasis was placed on developing strategies to incorporate these techniques into clinical trial design. This document reviews the literature, summarizes the topics discussed in the workshop, and provides recommendations for integration of these techniques into future clinical trial design.

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Clonotypic Light Chain Peptides Identified for Monitoring Minimal Residual Disease in Multiple Myeloma without Bone Marrow Aspiration.

Project description:BACKGROUND:Analytically sensitive techniques for measuring minimal residual disease (MRD) in multiple myeloma (MM) currently require invasive and costly bone marrow aspiration. These methods include immunohistochemistry (IHC), flow cytometry, quantitative PCR, and next-generation sequencing. An ideal MM MRD test would be a serum-based test sensitive enough to detect low concentrations of Ig secreted from multifocal lesions. METHODS:Patient serum with abundant M-protein before treatment was separated on a 1-dimensional SDS-PAGE gel, and the Ig light-chain (LC) band was excised, trypsin digested, and analyzed on a Q Exactive mass spectrometer by LC-MS/MS. We used the peptide's abundance and sequence to identify tryptic peptides that mapped to complementary determining regions of Ig LCs. The clonotypic target tryptic peptides were used to monitor MRD in subsequent serum samples with prior affinity enrichment. RESULTS:Sixty-two patients were tested, 20 with no detectable disease by IHC and 42 with no detectable disease by 6-color flow cytometry. A target peptide that could be monitored was identified in 57 patients (91%). Of these 57, detectable disease by LC-MS/MS was found in 52 (91%). CONCLUSIONS:The ability to use LC-MS/MS to measure disease in patients who are negative by bone marrow-based methodologies indicates that a serum-based approach has more analytical sensitivity and may be useful for measuring deeper responses to MM treatment. The method requires no bone marrow aspiration.

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B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients.

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Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial.

Project description:Minimal residual disease (MRD) by multiparameter flow cytometry (MFC) is the most effective tool to define a deep response in multiple myeloma (MM). We conducted an MRD correlative study of the EMN02/HO95 MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every 6 months during maintenance. Patients received high-dose melphalan (HDM) versus bortezomib-melphalan-prednisone (VMP) intensification, followed by bortezomib-lenalidomide-dexamethasone (VRd) versus no consolidation, and lenalidomide maintenance. Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based MFC protocols (eight colors, two tubes) with 10-4-10-5 sensitivity. At enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (HR 0.39; p < 0.001), 5-year overall survival was 86% versus 69%, respectively (HR 0.41; p < 0.001). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR 0.38;). In the 1-year maintenance MRD population, 42% of MRD-positive patients at pre-maintenance became MRD-negative after lenalidomide exposure. In conclusion, MRD by MFC is a strong prognostic factor. Lenalidomide maintenance further improved MRD-negativity rate.

| S-EPMC8175611 | biostudies-literature

Minimal residual disease analysis in myeloma - when, why and where.

Project description:The primary hurdle in the path to curing multiple myeloma (MM) is defining a validated minimal residual disease (MRD) and its utility in the therapeutic decision making. A better definition of MRD will aid in tailoring MM therapy further to address the clonal heterogeneity and genomic instability and overcome patient's ineffective immune surveillance. MRD analysis can define the logical endpoint for maintenance therapy, in addition also aids in providing a better clinical end point for studies comparing novel agents in myeloma. MRD is a surrogate for the survival in MM. Guidelines for global incorporation of MRD in myeloma are fraught with lack of standardization, universal availability and abridged physicians' understanding of MRD modalities. We aimed at addressing some of the frequently asked questions in the MRD assessment and will also place in perspective some arguments in favor of MRD assessment in routine practice and clinical trial scenario.

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