The current status of minimal residual disease assessment in myeloma

Kumar, Shaji; Rajkumar, S. Vincent

doi:10.1038/leu.2013.306

Cited by 16 publications

(12 citation statements)

References 19 publications

(28 reference statements)

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“…In recent years, quantification and characterization of this MRD has received more attention (39). It is now generally accepted that the detection of measurable MRD portends an ominous prognosis (4,5). …”

Section: Discussionmentioning

confidence: 99%

“…Lack of curative approaches is attributable to early and near-universal clonal heterogeneity (2,3) and the persistence of minimal residual disease post–traditional and novel therapies, including high-dose therapy with autologous stem cell rescue. Recent evidence has confirmed that detectable minimal residual disease (MRD) constitutes a harbinger for relapse and predicts adverse clinical outcomes (4,5). Thus, eradication of MRD is a priority in designing curative approaches against myeloma.…”

Section: Introductionmentioning

confidence: 99%

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Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma

Jensen

Rakhmilevich

Héninger

et al. 2015

Cancer Immunology Research

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Myeloma remains a virtually incurable malignancy. The inevitable evolution of multi-drug resistant clones and widespread clonal heterogeneity limit the potential of traditional and novel therapies to eliminate minimal residual disease, a reliable harbinger of relapse. Here we show potent anti-myeloma activity of macrophage-activating immunotherapy (αCD40+CpG) that resulted in prolongation of progression-free and overall survival in an immunocompetent, preclinically validated, transplant-based model of multi-drug resistant, relapsed/refractory myeloma (t-Vκ*MYC). αCD40+CpG was effective in vivo in the absence of cytolytic NK, T or B cells and resulted in expansion of M1-polarized (cytolytic/tumoricidal) macrophages in the bone marrow. Moreover, we show that concurrent loss/inhibition of TPL2 (Cot, MAP3K8), a MAP3K that is recruited to activated CD40 complex and regulates macrophage activation/cytokine production, potentiated direct, ex vivo anti-myeloma tumoricidal activity of αCD40+CpG-activated macrophages, promoted production of antitumor cytokine IL12 in vitro and in vivo and synergized with αCD40+CpG to further prolong progression-free and overall survival in vivo. Our results support the combination of αCD40-based macrophage activation and TPL2 inhibition for myeloma immunotherapy. We propose that αCD40-mediated activation of innate antitumor immunity may be a promising approach to control/eradicate minimal residual disease following cytoreduction with traditional or novel anti-myeloma therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma

Jensen

Rakhmilevich

Héninger

et al. 2015

Cancer Immunology Research

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“…The past decade has seen extraordinary advances in the treatment of MM, particularly with the discovery of proteasome inhibitors (such as bortezomib) and immunomodulatory agents (such as lenalidomide), that have become the pillars of frontline treatment regimens . Furthermore, with an explosion of novel agents (including carfilzomib, pomalidomide, ixazomib, daratumumab, elotuzumab, and panobinostat), most of them already FDA and EMA approved, for use in the relapsed/refractory (R/R) setting, the overall response rates (ORR), progression‐free survival (PFS) and overall survival (OS) have dramatically improved …”

Section: Introductionmentioning

confidence: 99%

A rare case of multiple myeloma with intracranial extramedullary relapse: One or more myeloma clones?

Markovic

Calafiore

Martino

et al. 2019

Clinical Case Reports

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“…Recently, the survival rate has been increasing due to the development of various types of new drugs and the therapeutic options for MM have been characterized by proteasome inhibitors (bortezomib and carfilzomib) and thalidomide analogs [3, 4]. However, MM still remains an incurable cancer, since most MM patients eventually develop drug resistance and die from the disease [5]. …”

Section: Introductionmentioning

confidence: 99%

Chromothripsis in Treatment Resistance in Multiple Myeloma

Lee

Yoon

et al. 2017

Genomics Inform

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Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, β-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients’ results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM.

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The current status of minimal residual disease assessment in myeloma

Cited by 16 publications

References 19 publications

Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma

Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma

A rare case of multiple myeloma with intracranial extramedullary relapse: One or more myeloma clones?

Chromothripsis in Treatment Resistance in Multiple Myeloma

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