Measurable residual disease assessed by mass spectrometry in peripheral blood in multiple myeloma in a phase II trial of carfilzomib, lenalidomide, dexamethasone and autologous stem cell transplantation

Derman, Benjamin A.; Stefka, Andrew; Jiang, Ken; McIver, Amanda; Kubicki, Tadeusz; Jasielec, Jagoda; Jakubowiak, Andrzej

doi:10.1038/s41408-021-00418-2

Cited by 45 publications

(33 citation statements)

References 14 publications

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“…Currently, the field is still developing these techniques and evaluating how to best use them. Some studies comparing mass spectrometry results to bone-marrow-based MRD assays have found that the M -protein can be detected when BM-based tests are negative (53)(54)(55)(56). And, a recent study found LC-MS to be a better predictor of PFS (56)…”

Section: Mass Spectrometry Methodsmentioning

confidence: 99%

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration

Anderson

Auclair

Adam

et al. 2021

Clinical Cancer Research

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The pace of advances in targeted and immune therapies in Multiple Myeloma (MM) is unprecedented.To keep this momentum going, a framework is proposed outlining key elements and regulatory considerations that will delineate how Minimal Residual Disease (MRD) data could be collected to help standardize correlative analyses across clinical studies. The framework is intended for use by sponsors to incorporate into ongoing or planned trials, without compromising or interrupting their primary trial objectives. Also covered are technologies already impacting MRD assessment in myeloma and emerging approaches that sponsors should consider including in their trials. The current value of MRD to inform clinical care is presented using real world cases of patients with smoldering MM, newly diagnosed transplant eligible and ineligible, and relapse refractory disease, with each case summarizing what is known and questions to be addressed in clinical studies.Research.

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Section: Mass Spectrometry Methodsmentioning

confidence: 99%

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration

Anderson

Auclair

Adam

et al. 2021

Clinical Cancer Research

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“…MASS-FIX was neither intended nor specifically designed for MRD assessment. Researchers have developed MS-based methods 3,4,[31][32][33] that look for clonotypic peptides of the M-protein for MRD assessment. These targeted methods have an order of magnitude lower limit of detection for M-protein when compared with MASS-FIX.…”

Section: Discussionmentioning

confidence: 99%

Detection of Plasma Cell Disorders by Mass Spectrometry: A Comprehensive Review of 19,523 Cases

Dasari

Kohlhagen

Dispenzieri

et al. 2022

Mayo Clinic Proceedings

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Objectives: To verify the analytical performance of a new mass spectrometryebased method, termed MASS-FIX, when screening for plasma cell disorders in a routine clinical laboratory. Patients and Methods: Results from 19,523 unique patients tested for an M-protein between July 24, 2018, and March 6, 2020, by a combination serum protein electrophoresis (SPEP) and MASS-FIX were examined for consistency with pretest implementation performance. MASS-FIX's ability to verify abnormal results from SPEP and free light chain measurements was then compared with that of immunofixation electrophoresis (IFE) using a separate cohort of 52,586 patients tested by SPEP/IFE during the same period. Results: Overall, 62.4% of our cohort was negative for an M-protein. Importantly, 7.3% of all specimens had an M spike on SPEP (0.1 to 8.5 g/dL) and MASS-FIX detected an M-protein in all these samples. Of all samples, 30.3% had M-proteins that were detected by MASS-FIX but the SPEP finding was too small for quantification. Of the positive samples, 5.7% contained a therapeutic monoclonal antibody. Of the positive samples, 4.1% had an N-glycosylated light chain (biomarker of high-risk plasma cell disorders). MASS-FIX confirmed a higher percentage of SPEP abnormalities than IFE. MASS-FIX was slightly more sensitive than IFE when confirming an M-protein in samples with an abnormal free light chain ratio. MASS-FIX had a very low sample repeat rate (1.5%). MASS-FIX was highly automatable resulting in a higher number of samples/technologist/day than IFE (w30% more). Conclusion: Overall, MASS-FIX was successful in maintaining validation characteristics. MASS-FIX was more sensitive in confirming SPEP abnormalities when compared with IFE. Ability to detect therapeutic monoclonal antibodies and glycosylated light chains was distinctly advantageous.

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“…Moreover, circulating micro-193a-5p may serve as a predictive marker of early relapse after autologous stem cell transplantation in MM patients [118]. Most recently, mass spectroscopy has been proposed as a complementary approach for the assessment of the MRD status in the peripheral blood [119,120]. Of note, a significant correlation of the MRD negativity determined by NGF in bone biopsies and by MALDI-TOF in the peripheral blood was reported at ASCO 2021 [121,122].…”

Section: Assessment Of Mrd For Clinical Decision-making and Personalized Targeted Therapies In Rrmmmentioning

confidence: 99%

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond

Podar

Leleu

2021

Cancers

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Despite the challenges imposed by the COVID-19 pandemic, exciting therapeutic progress continues to be made in MM. New drug approvals for relapsed/refractory (RR)MM in 2020/2021 include the second CD38 monoclonal antibody, isatuximab, the first BCMA-targeting therapy and first-in-class antibody–drug conjugate (ADC) belantamab mafodotin, the first BCMA-targeting CAR T cell product Idecabtagen-Vicleucel (bb2121, Ide-Cel), the first in-class XPO-1 inhibitor selinexor, as well as the first-in-class anti-tumor peptide-drug conjugate, melflufen. The present introductory article of the Special Issue on “Advances in the Treatment of Relapsed and Refractory Multiple Myeloma: Novel Agents, Immunotherapies and Beyond” summarizes the most recent registration trials and emerging immunotherapies in RRMM, gives an overview on latest insights on MM genomics and on tumor-induced changes within the MM microenvironment, and presents some of the most promising rationally derived future therapeutic strategies.

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Measurable residual disease assessed by mass spectrometry in peripheral blood in multiple myeloma in a phase II trial of carfilzomib, lenalidomide, dexamethasone and autologous stem cell transplantation

Cited by 45 publications

References 14 publications

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration

Detection of Plasma Cell Disorders by Mass Spectrometry: A Comprehensive Review of 19,523 Cases

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond

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