Clinical value of measurable residual disease testing for multiple myeloma and implementation in Japan

Abstract

The development of novel therapeutic agents has led to an increase in patients with multiple myeloma (MM) who achieve a complete response (CR). Consequently, a good correlation has been established between the CR rate and progression-free survival, and new methods are needed to stratify CR cases based on the measurable residual disease (MRD) and thus predict prognosis. Previously, multiparameter flow cytometry (MFC), which is rapid and widely available, has been used to assess MRD in patients with MM. Although the EuroFlow next-generation flow method was developed as a highly sensitive and standardized method of MRD detection, the procedure is costly within the current Japanese public medical insurance system. Recently, two Japanese clinical laboratory test companies, SRL and BML, respectively developed new and inexpensive 8-and 10-color single-tube MFC methods intended for the assessment of MRD under the current Japanese public medical insurance system. In this article, I have reviewed the most recent updates on MRD monitoring protocols in Japan and the clinical trials of the use of this parameter in patients with MM.

Perspective: sensitive detection of residual lymphoproliferative disease by NGS and clonal rearrangements—how low can you go?

“…Aiming at a number of reads lower than that required by the desired sensitivity [32] or not reporting the number of reads [31] poses a problem when evaluating the assay. Reviewing NGS, Takamatsu argued that the PCR products are sequenced at least 10 6 times using high-throughput NGS to achieve MRD detection of one in a million [43]. Contrary to the reasoning in an earlier article on monitoring FLT3-ITD and NPM1 mutations [24], 10,000 sequencing reads do not equal a sensitivity of 10 −4 , nor do a million reads confidently reveal one in a million cells (see also [22,24,44]).…”

Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma

“…Secondary endpoints included: PFS (defined as the period between the first dose of injectable PI-based therapy until the date of confirmed PD or death due to any cause, whichever occurred first) by Kaplan-Meier analysis, with dropouts treated as censoring; OS (defined as the period between the first dose of injectable PI-based therapy until the date of death due to any cause); rate of minimal residual disease (MRD) negativity in bone marrow (BM) in patients who achieved complete response (CR), with MRD negativity defined as the absence of tumour plasma cell within 100 000 BM cells (i.e. <10 -5 ) by single-tube 8-colour multiparameter flow cytometry (MFC) method (SRL-Flow) [ 13 ] or 1 000 000 BM cells (i.e. <10 -6 ) by adaptive next-generation sequencing (NGS) [ 14 ]; best response (CR, very good partial response [VGPR], partial response [PR], MR, stable disease, PD); overall response rate (ORR; the proportion of patients achieving ≥PR); the proportion of patients achieving VGPR or better; duration of response (DOR; defined as the period between the date of first PR or better and the earliest date of PD or death due to any cause); time to next treatment (TTNT), defined as the period between the first dose of injectable PI-based therapy to the date of the next antitumor treatment or death due to any cause, whichever occurred first; health-related quality of life (HRQOL) and Quality Adjusted Life Years (QALY); healthcare resource utilization (HCRU), including the length of hospital stay and outpatient visits (per person-month) during the initial 3 cycles of injectable PI-based therapy and following IRd treatment; relative dose intensity (RDI) for each IRd study drug (see Online Resource 2 for full description); and safety.…”

TLR7/8 agonist treatment induces an increase in bone marrow resident dendritic cells and hematopoietic progenitor expansion and mobilization

“…Aiming at a lower number of reads than required by the desired sensitivity [32] or not reporting the number of reads [31] poses a problem when evaluating the assay. Reviewing NGS, Takamatsu argues that the PCR products are sequenced at least 10 6 times using high-throughput NGS to achieve MRD detection of one in a million [43]. Contrary to the reasoning in an earlier paper on monitoring FLT3-ITD and NPM1 mutations [24] 10,000 sequencing reads do not equal a sensitivity of 10 -4 , nor do a million reads confidently reveal one in a million cells (see also [22,24,44].…”