MRD IN ALL

MRD IN MULTIPLE MYELOMA

Going deeper by measuring MRD

In ALL, measurable residual disease (MRD) is defined as the presence of detectable leukemic cells within the bone marrow during morphologic CR.⁵ The definition of MRD positivity has yet to be standardized, but a sensitivity threshold of 10^-4 (or 0.01%, 1 cancer cell in 10,000 normal cells) is commonly used and may guide clinical outcomes.⁶

A substantial proportion of adult patients with ALL relapse despite achieving morphologic CR, with a reported relapse rate of 40%–50%.⁷ Furthermore, patients may still have detectable residual disease despite achieving CR with morphological testing.⁸

• Approximately 30%–40% of patients who achieve CR may still test positive for MRD^1,9,10,*

MRD as a prognostic indicator

Measurable residual disease (MRD) is a strong prognostic indicator for survival outcomes and relapse in ALL.^3,8

• In a meta-analysis (N=13,637), the presence of MRD after induction or consolidation therapy was associated with negative outcomes.^3,† A significant benefit was seen in overall survival (OS) in adult and pediatric patients with ALL who achieved MRD negativity³

• Additionally, a retrospective study observed that MRD positivity at the time of allogeneic hematopoietic stem cell transplantation (HSCT) in first CR was significantly associated with hematologic relapse^11,‡

Cumulative incidence of hematologic relapse based on MRD status¹¹

Detecting MRD

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for ALL state that a bone marrow sample from the first or early small-volume (up to 3 mL) pull is preferred for measurable residual disease (MRD) testing.¹²

There are 3 common techniques used to quantify MRD in ALL:¹³

NCCN Guidelines^® recommend testing for MRD

NCCN Guidelines state that measurable residual disease (MRD) is an essential component of patient evaluation over the course of sequential therapy in pediatric and adult patients with ALL.^12,15,**

MRD testing timeline^12,15  

Get more facts about MRD testing for your practice

An infographic resource that provides an overview of measurable residual disease (MRD) in ALL, including facilities that conduct MRD testing.

DOWNLOAD THE GO DEEPER BY MEASURING MRD INFOGRAPHIC

A fact sheet with more information about MRD in ALL, including various detection methods.

DOWNLOAD THE MEASURABLE RESIDUAL DISEASE AND ACUTE LYMPHOBLASTIC LEUKEMIA FACT SHEET

A list of CLIA-certified external facilities that test for MRD in ALL.

DOWNLOAD THE FACILITIES CONDUCTING MRD TESTING LIST

A video that discusses optimal sampling and guideline recommendations for MRD testing in ALL by Dr. Kanagal.

WATCH THE MRD IN ALL VIDEO

Watch the following videos to learn about MRD in B-Cell Precursor ALL

This episode provides an overview of the objectives of the video series.

WATCH EPISODE 1

This episode covers the definition, prognostic value, and economic impact of MRD.

WATCH EPISODE 2

This episode covers keys to successful testing and methods of MRD detection.

WATCH EPISODE 3

This episode covers how to interpret MRD results and provides a summary of clinical implications and future applications.

WATCH EPISODE 4

This episode covers hypothetical patient cases that demonstrate the clinical utility of MRD testing.

WATCH EPISODE 5

*Range based on three clinical studies in which MRD was measured at different time points.^1,9,10

^†According to a meta-analysis of 39 publications of distinct studies with 13,637 patients.³

^‡According to a retrospective study evaluating the cumulative incidence of hematologic relapse in 257 patients with Ph(+) ALL who underwent HSCT in first CR.¹¹

^§A baseline sample is only needed for Ig/TCR gene rearrangements. A baseline sample is not required for abnormal gene fusions.¹³

**AYA patients can be included in either pediatric or adult patient populations.^12,15

^††Dependent on MRD testing technique used.^12,15

^‡‡Additional time points should be guided by the regimen used. Serial monitoring frequency may be increased in patients with molecular relapse or persistent low-level disease burden.^12,15

^§§Additional time points should be guided by the regimen used.¹⁵

***MRD testing may be included with a bone marrow aspirate.¹⁵

Clinical relevance of MRD

Minimal residual disease (MRD) in multiple myeloma refers to the presence of residual myeloma cells in the bone marrow after an observed response.^2,4 The 2016 International Myeloma Working Group (IMWG) consensus criteria recommends a minimum sensitivity of 10^-5 when defining MRD negativity.⁴ The presence of MRD may lead to disease progression and relapse in multiple myeloma.⁴

MRD as a prognostic indicator

Minimal residual disease (MRD) is a prognostic indicator for survival outcomes in multiple myeloma.¹⁶

• In a meta-analysis, MRD negativity was associated with improved PFS (n=1,273) and OS (n=1,100) in patients with multiple myeloma^{16,†††,‡‡‡}

• Additionally, a recent meta-analysis of 6 studies (N=3,283) in patients with newly diagnosed multiple myeloma (NDMM) observed that MRD negativity was associated with improved PFS, supporting MRD as a surrogate endpoint for PFS in clinical trials^17,§§§

Detecting MRD

There are several techniques used to quantify minimal residual disease (MRD) in multiple myeloma:

Applications of MRD in multiple myeloma

Response criteria in multiple myeloma has evolved over the years with advances in therapy.⁴

The International Myeloma Working Group (IMWG) consensus criteria for response and minimal residual disease (MRD) assessment was published in 2016, which defines categories of MRD negativity:⁴

• Sustained MRD negative
• Flow MRD negative
• Sequencing MRD negative
• Imaging-positive MRD negative

Continued research will help establish the role of MRD in the treatment continuum of multiple myeloma.⁴

Get an overview of MRD in multiple myeloma

Watch this video for an overview of minimal residual disease (MRD) in multiple myeloma.

Learn more about MRD in hematologic malignancies, including ALL and multiple myeloma, with this brochure.

DOWNLOAD THE MINIMAL RESIDUAL DISEASE IN HEMATOLOGIC MALIGNANCIES BROCHURE

Learn more about the prognostic and therapeutic implications of MRD in acute myeloid leukemia (AML).

DOWNLOAD THE MEASURABLE RESIDUAL DISEASE IN AML FACT SHEET

^†††According to a meta-analysis of 14 studies that provided data on the impact of MRD on PFS in 1,273 patients with multiple myeloma, and 12 studies on OS in 1,100 patients with multiple myeloma.¹⁶

^‡‡‡MRD was measured using the following methods: MFC, ASO-qPCR, or NGS. However, analysis was restricted to techniques with a limit of detection of 0.01% or lower.¹⁶

^§§§MRD was measured using the following methods: 8-color FCM, 7-color FCM, 4-color FCM, MFC, NGS, and NGF.¹⁷

ASO, allele-specific oligonucleotide; AYA, adolescent and young adult; BCI, Bayesian credible interval; CLIA, Clinical Laboratory Improvement Amendments; CT, computed tomography; FCM, flow cytometry; HR, hazard ratio; Ig, immunoglobulin; MFC, multiparametric flow cytometry; N/A, not applicable; NCCN, National Comprehensive Cancer Network; NGF, next-generation flow; NGS, next-generation sequencing; PCR, polymerase chain reaction; PET, positron emission tomography; PFS, progression-free survival; Ph(+), Philadelphia chromosome–positive; qPCR, quantitative polymerase chain reaction; TCR, T-cell receptor; VDJ, variable diversity joining.