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IntroductionThe measurement of minimal residual disease (MRD) with clonoSEQ® can be used in the assessment of B-cell lymphoid tumor burden throughout treatment with accuracy, sensitivity and standardization when compared to traditional cytomorphology. With the approval of novel treatments, standardized MRD assessment with improved performance is in...
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Context 1
... outcomes calculated in the model are OS and PFS, shown in the form of curves. Input values for both outcome curves with the related negative exponential coefficient and the exponential intercept, expressed in months, were chosen for MRD positivity, negativity, and relapsed state, and are shown in Tables 1 and 2. ...Context 2
... no MRD testing, mean total costs are €452,626, with a range from €293,009 as lowest to €482,138 as highest costs. Mean incremental costs for MRD testing using clono-SEQ Ò versus no MRD testing over 10 years are -€60,033, with a range from -€92,080 to -€35,731 ( Fig. 3 and Table 1a, see Supplementary Material). The mean incremental costs per patient in 1 year are -€17,553, with a range from -€24,052 to -€11,862. ...Context 3
... a period of 3 years, mean incremental costs are -€54,654, with a range from -€84,756 to -€32,883. For the time horizons of 1 and 3 years, the mean totals costs for no MRD testing lie outside the confidence range (Table 1a, see Supplementary Material). ...Context 4
... increase of 5% in the baseline MRD positivity rate leads to an increase of about €8,900 in total costs for MRD testing per patient and to an increase of about €100 in total costs for no MRD testing. The decrease in total incremental costs is about €8,800 per 5% increase in the MRD positivity rate (Table 1b, see Supplementary Material). ...Context 5
... prolongation of the interval of MRD assessment from 3 to 6 months leads to a decrease of about €8,500 in total costs for MRD testing per patient. Total costs for no MRD testing remain on a stable level of about €452,000 to €453,000 at all assessment intervals (Table 1c, see Supplementary Material). For a period of 3 years, the cost impact depending on the MRD assessment interval shows the same pattern. ...Context 6
... prolongation of the assessment interval from 3 to 6 months leads to a decrease of about €9,100 in total costs for MRD testing per patient. The total costs for no MRD testing remain on a level of €256,000 to €257,000 for all assessment intervals but lie outside the confidence range (Table 1d, see Supplementary Material). ...Citations
... The study estimated that using NGS may save €18,396 in 1 year, €69,991 after 3 years, and €77,140 after 10 years per patient for treatment in those who are tested for MRD versus those not tested, because healthcare providers can avoid unnecessary and costly MM treatment if MRD status is known. 60 A streamlined process of MRDdirected therapy that would likely be covered by payers may incentivize hospitals to invest in upgrading their testing facilities. ...
We used a modified Delphi approach to establish areas of consensus and nonconsensus regarding the utility of determining measurable residual disease (MRD) to assess multiple myeloma (MM) treatment response, which may inform disease management and design of future clinical trials. This modified Delphi study incorporated 2 iterative rounds of surveys to evaluate the opinions of an expert panel of 61 practicing hematological oncologists from across 14 countries in Europe concerning the use of MRD testing in MM management. Survey 1 assessed experts’ opinions on MRD testing in different clinical situations and associated challenges. Survey 2 focused on the lack of consensus areas identified in survey 1. Consensus to an individual question was defined a priori as 75% agreement or disagreement by the panel. From the 2 rounds of surveys, the experts reached consensus agreement that MRD testing should be performed in newly diagnosed or relapsed patients who achieved complete response (CR) or better after transplantation. In transplant-ineligible patients, experts recommended MRD testing in those who are ≤70 years old and in CR. If a patient was previously positive on positron-emission tomography and computed tomography (PET/CT), both MRD and PET/CT should be assessed at CR. MRD testing should be performed ≤6 months after transplantation and every 6–12 months in continuously treated patients in CR. There was no consensus on making treatment decisions based on MRD status. MRD testing is an important component of clinical management in MM. Additional data will further clarify the role of MRD in guiding treatment decisions.
... Although no cost-effectiveness analysis about MRD testing in CLL has been published, there is a report about NGS in multiple myeloma [78] that suggests that therapy guided by MRD status could actually be less expensive than no testing due to the costs saved during therapy free periods driven Current Treatment Options in Oncology by uMRD status. Furthermore, MFC, which is commonly available in most academic institutions, is a less expensive method with a sensitivity of 10 −4 to 10 −6 . ...
Opinion statement
Treatment of chronic lymphocytic leukemia (CLL) has evolved dramatically during the last decade, from chemoimmunotherapy (CIT)-based therapies to newer B-cell receptor (BCR) signaling targeting agents, which are sometimes given as continuous schemes. Response to treatment was traditionally defined according to clinical variables designed to assign a response category. Interest in assessing for deeper responses in CLL by the means of measurable residual disease (MRD) testing has been the subject of research during the last several years. Analyses and sub-analyses of clinical trials have shown that achieving undetectable MRD (uMRD) in CLL is an important prognostic factor. In this review, we summarize the available evidence about MRD in CLL, from the various assays available for measurement, the compartment to test, the impact of reaching uMRD according to the treatment regimen, and the results of fixed duration treatment guided by MRD trials. Finally, we summarize how MRD can be incorporated in clinical practice and how it may guide fixed duration treatment in the future should evidence continue to accumulate in that direction.
... According to a recent study comparing the financial burden of multiple myeloma patients in Germany with Clon-oSeq MRD measurement to those without MRD measurement, this method could save 18,396 Euros per patient in 1 year and 77,140 in 10 years [98]. ...
Purpose of Review
Measurable residual disease (MRD) is an important monitoring parameter that can help predict survival outcomes in acute lymphoblastic leukemia (ALL). Identifying patients with MRD has the potential to decrease the risk of relapse with the initiation of early salvage therapy and to help guide decision making regarding allogeneic hematopoietic cell transplantation. In this review, we discuss MRD in ALL, focusing on advantages and limitations between MRD testing techniques and how to monitor MRD in specific patient populations.
Recent Findings
MRD has traditionally been measured through bone marrow samples, but more data for evaluation of MRD via peripheral blood is emerging. Current and developmental testing strategies for MRD include multiparametric flow cytometry (MFC), next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and ClonoSeq. Novel therapies are incorporating MRD as an outcome measure to demonstrate efficacy, including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T (CAR-T) cell therapy.
Summary
Understanding how to incorporate MRD testing into the management of ALL could improve patient outcomes and predict efficacy of new therapy options.
... Cost effectiveness models suggest that MRD-guided maintenance discontinuation is likely to be cost effective due to the reduced expenditure on high-cost drugs. 85,86 The impact of this strategy on patient outcomes remains an active area of research and is being investigated in multiple ongoing clinical trials. Treatment escalation or de-escalation based on MRD or MS response assessments is therefore not yet standard of care. ...
Mass spectrometry (MS) techniques provide a highly sensitive methodology for the assessment and monitoring of paraproteins compared to standard electrophoretic techniques. The International Myeloma Working Group (IMWG) recently approved the use of intact light chain matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry (MALDI‐TOF MS) in lieu of immunofixation in the clinical assessment of patients and the assessment of patients enrolled on clinical trials. The increased sensitivity of these assays may help to detect and monitor monoclonal proteins (MP) in many patients with previously non‐measurable disease, will reduce complete response (CR) rates and increase detection of low‐level MP. The ability to track the unique mass or amino acid sequence of the MP also eliminates interference from therapeutic monoclonal antibodies (tmAbs) in most patients with IgG kappa myeloma. The intact light chain assays also provide structural information about the monoclonal light chain, including the presence of N‐linked glycosylation, which has been shown to be commoner on amyloidogenic light chains and may have prognostic significance in monoclonal gammopathy of undetermined significance (MGUS). In this review, we discuss these issues alongside differences in the analytical and practical aspects related to the different MS assays under development and the challenges for MS.
Minimal residual disease (MRD) assessment using peripheral blood instead of bone marrow aspirate/biopsy specimen or the biopsy of the cancerous infiltrated by lymphoid malignancies is an emerging technique with enormous interest of research and technological innovation at the current time. In some lymphoid malignancies (particularly ALL), Studies have shown that MRD monitoring of the peripheral blood may be an adequate alternative to frequent BM aspirations. However, additional studies investigating the biology of liquid biopsies in ALL and its potential as an MRD marker in larger patient cohorts in treatment protocols are warranted. Despite the promising data, there are still limitations in liquid biopsies in lymphoid malignancies, such as standardization of the sample collection and processing, determination of timing and duration for liquid biopsy analysis, and definition of the biological characteristics and specificity of the techniques evaluated such as flow cytometry, molecular techniques, and next generation sequencies. The use of liquid biopsy for detection of minimal residual disease in T-cell lymphoma is still experimental but it has made significant progress in multiple myeloma for example. Recent attempt to use artificial intelligence may help simplify the algorithm for testing and may help avoid inter-observer variation and operator dependency in these highly technically demanding testing process.
Aims
The goal of this study was to review the economic evaluations of health technologies in multiple myeloma (MM) and provide guidance and recommendations for future health economic analyses.
Materials and methods
A systemic literature review (SLR) was conducted on original economic assessment studies and structured review papers focusing on the studies in MM. The search was limited to English language papers published from 1 January 2000 onwards. Publications not applying any type of modelling methodology to describe disease progression and patient pathways over a specific time horizon were excluded.
Results
A total of 2,643 publications were initially identified, of which 148 were eligible to be included in the full-text review phase. From these, 49 publications were included in the final analysis. Most published health economic analyses supported by models came from high-income countries. Evaluations from middle-income countries were rarely published. Diagnostic technologies were rarely modelled and integrated care had not been modelled. Very few models investigated MM treatments from a societal perspective and there was a relative lack of evaluations regarding minimal residual disease (MRD).
Limitations
Limitations of the publications included differences between trial populations and modelled populations, justification of methods, lack of confounder analyses, and small trial populations. Limitations of our study included the infeasibility of comparing MM economic evaluations due to the significant variance in modelled therapeutic lines and indications, and the relative scarcity of published economic evaluations from non-high-income countries.
Conclusions
As published economic models lacked many of the elements of the complex and heterogeneous patient pathways in MM and they focused on single decision problems, a thorough, open-source economic whole disease modelling framework is needed to assess the economic value of a wide range of technologies across countries with various income levels with a more detailed view on MM, by including patient-centric and societal aspects.
