Association of Minimal Residual Disease Negativity Rates With Progression Free Survival in Frontline Therapy Trials for Newly Diagnosed Multiple Myeloma: A Meta-analysis

Ficek, Joseph; Yuan, Shuai; Kalaitzaki, Eleftheria; Tosolini, Alessandra; Du, Ling; Kremer, Brandon E.; Davy, Katherine; Zhou, Helen; Chen, Tai-Tsang

doi:10.1016/j.clml.2023.02.005

Cited by 5 publications

(3 citation statements)

References 35 publications

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“…Thus, MRD-negative rates in MM randomized clinical trials are moderately correlated with a treatment effect in PFS. The R 2 trial observed in this study is inferior to the 0.97 reported in a previous study using data from 6 trials 19 and slightly superior to the 0.62 of a recent meta-analysis of 13 trials, 20 some of which using MRD methods other than NGF and NGS. Thus, the improved sensitivity and specificity of next-generation methods may be paramount for a more accurate prediction of treatment effect based on MRD-negative rates.…”

contrasting

confidence: 89%

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Impact of treatment effect on MRD and PFS: an aggregate data analysis from randomized clinical trials in multiple myeloma

Paiva,

Zherniakova,

Nuñez-Córdoba

et al. 2023

Blood Advances

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contrasting

confidence: 89%

“… 18 However, the role of MRD as a surrogate of treatment efficacy for potential use as an end point in clinical trials, remains uncertain. 19 , 20 …”

mentioning

confidence: 99%

Impact of treatment effect on MRD and PFS: an aggregate data analysis from randomized clinical trials in multiple myeloma

Paiva,

Zherniakova,

Nuñez-Córdoba

et al. 2023

Blood Advances

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“…One prognostic marker that is already emerging as a potentially important way of guiding treatment escalation or de-escalation, including the use of deferred HDM-ASCT, is MRD status. Achieving MRD negativity has been demonstrated to be one of the key prognostic factors for long-term PFS and OS in patients with NDMM and a potential surrogate for outcomes [65][66][67][68][69]. Moreover, achieving sustained MRD negativity is highly correlated with prolonged PFS and OS [70][71][72][73][74] and is associated with better prognosis than simply achieving MRD-negative status; for example, an analysis of 23 patients with NDMM who were receiving lenalidomide maintenance following HDM-ASCT (n = 10) or induction therapy (n = 13) showed that patients who lost or were unable to obtain an MRD-negative status during the first year of maintenance were 14 times more likely to have disease progression than those with a sustained MRD-negative status for 1 year [70].…”

Section: Depth Of Response and Rate Of Mrd Negativity With Quadruplet...mentioning

confidence: 99%

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Mo,

Hartley-Brown,

Midha

et al. 2023

Cancers

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The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT.

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Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma

Guerrero,

Puig,

Cedena

et al. 2024

Blood

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The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD in order to avoid undertreating them. Here, we studied 267 newly-diagnosed transplant-eligible MM patients enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International staging system (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having none versus one versus two or more risk factors (ISS 3, ≥0.01% CTCs and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33% and 57%, respectively (P<.001). Thus, these easily measurable risk factors could help refining the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. Registered at www.clinicaltrials.gov with respective identifiers NCT01916252 and NCT02406144.

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Association of Minimal Residual Disease Negativity Rates With Progression Free Survival in Frontline Therapy Trials for Newly Diagnosed Multiple Myeloma: A Meta-analysis

Cited by 5 publications

References 35 publications

Impact of treatment effect on MRD and PFS: an aggregate data analysis from randomized clinical trials in multiple myeloma

Impact of treatment effect on MRD and PFS: an aggregate data analysis from randomized clinical trials in multiple myeloma

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma

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