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

Oliva, Stefania; Bruinink, Davine Hofste op; Říhová, Lucie; D’Agostino, Mattia; Pantani, Lucia; Capra, Andréa; Troia, Rossella; Petrucci, Maria Teresa; Villanova, Tania; Všianská, Pavla; Jugooa, Romana; Brandt-Hagens, Claudia; Gilestro, Milena; Offidani, Massimo; Ribolla, Rossella; Galli, Mónica; Gay, Francesca; Cavo, Michèle; Omedè, Paola; Velden, Vincent H.J. van der; Boccadoro, Mario; Sonneveld, Pieter

doi:10.1038/s41408-021-00498-0

Cited by 32 publications

(29 citation statements)

References 39 publications

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“…After a median follow-up of 74.8 months, consolidation was associated with a significantly prolonged PFS (median 59.3 months vs. 42.9 months, HR = 0.81, p = 0.016) with OS not reached in both arms despite OS curve separation after 5–6 years in favor of consolidation [ 62 ]. Remarkably, in patients with MRD negativity after consolidation, median PFS was 87 months vs. 38 months in MRD positive (HR = 0.39, p < 0.001), whereas 5-year OS was 82% vs. 69%, respectively (HR = 0.51, p = 0.01) [ 63 ]. On the other hand, the phase III BMT CTN00702 STaMINA trial failed to demonstrate a benefit of consolidation therapy [ 64 ].…”

Section: Where We Are With Consolidation Therapy Post-asctmentioning

confidence: 99%

Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

Morè

Corvatta²,

Manieri

et al. 2022

Cells

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The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients.

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Section: Where We Are With Consolidation Therapy Post-asctmentioning

confidence: 99%

Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

Morè

Corvatta²,

Manieri

et al. 2022

Cells

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“…The high and independent prediction accuracy of EuroFlow-NGF, for both OS and PFS, was recently demonstrated in a Spanish prospective study including more than 400 newly diagnosed MM patients; in this large cohort, only 7% of patients without a detectable disease (reported sensitivity of 10 −6 ) relapsed, predominantly with extramedullary disease [ 127 ]. Consistently, in the EMN02/HOVON 95 MM trial, patients with sustained MFC-MRD negativity (sensitivity of 10 −4 –10 −5 ) had a 5-year PFS and OS of 81% and 94%, respectively, thus suggesting that MRD negativity can be used as a surrogate endpoint for survival outcomes [ 128 ].…”

Section: Multiple Myeloma (Mm)mentioning

confidence: 87%

Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges

Riva¹,

Nasillo²,

Ottomano³

et al. 2021

Cancers

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Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the clinical management of hematologic malignancies, enabling valuable post-therapy risk stratifications and guiding risk-adapted therapeutic approaches. However, specific prognostic values of MRD in different hematological settings, as well as its appropriate clinical uses (basically, when to measure it and how to deal with different MRD levels), still need further investigations, aiming to improve standardization and harmonization of MRD monitoring protocols and MRD-driven therapeutic strategies. Currently, MRD measurement in hematological neoplasms with bone marrow involvement is based on advanced highly sensitive methods, able to detect either specific genetic abnormalities (by PCR-based techniques and next-generation sequencing) or tumor-associated immunophenotypic profiles (by multiparametric flow cytometry, MFC). In this review, we focus on the growing clinical role for MFC-MRD diagnostics in hematological malignancies—from acute myeloid and lymphoblastic leukemias (AML, B-ALL and T-ALL), to chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)—providing a comparative overview on technical aspects, clinical implications, advantages and pitfalls of MFC-MRD monitoring in different clinical settings.

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“…A growing number of opinions are claiming the recognition of MRD negativity as a primary end-point for efficacy in clinical trials (65)(66)(67)(68). Additionally, many studies have confirmed the prognostic power of MRD kinetics based on the evidences obtained during the maintenance phase of treatment at the frontline (69)(70)(71).…”

Section: The Settlement Of Measurable Residual Disease In Clinical Pr...mentioning

confidence: 99%

Tumor Reduction in Multiple Myeloma: New Concepts for New Therapeutics

Alonso

Lahuerta

2022

Front. Oncol.

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The development of new resources for a more accurate diagnosis and response assessment in multiple myeloma has been a long process for decades, mainly since the middle of the 20th century. During this time, the succession of technical advances has run parallel to the better knowledge of disease biology and the availability of novel therapeutic strategies. The cornerstone of standardized criteria to uniformly evaluate the disease response in myeloma dates back to the 1990s when the key role of complete remission was established. Since then, different updates have been implemented according to available scientific evidences not always without certain controversies. The progressive improvements in survival results of myeloma patients and the growing quality of responses due to the novel therapies have led to the need of developing new tools for better monitoring of tumor burden. In this way, the concept of minimal residual disease and its key value based on the prognostic significance and the clinical relevance has been consolidated during the last years, overcoming the value of conventional response criteria or classical adverse prognosis markers. Nevertheless, its precise role in the clinical management of myeloma patients to detect early treatment failure and trigger early rescue strategies is still pending to be defined. In this review, we revisit the major milestones in the understanding of tumor reduction in multiple myeloma until the most recent imaging techniques or liquid biopsy approaches, including a critical view of conventional response criteria, whose backbone has remained unchanged during the last 20 years.

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

Cited by 32 publications

References 39 publications

Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges

Tumor Reduction in Multiple Myeloma: New Concepts for New Therapeutics

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