Minimal residual disease in multiple myeloma: why, when, where

Yee, Andrew J.; Raje, Noopur

doi:10.1182/hematology.2021000230

Cited by 13 publications

(11 citation statements)

References 73 publications

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“…Taken together, our preliminary validation studies of two technical modifications of molecular and cell-based assays for detecting MM in the pB support a future perspective to develop gradual follow-up concepts for MM patients that schedule investigations of BM samples only when there is no evidence of disease in the pB. However, the pilot study presented here clearly is not sufficient to boost the so far only emerging clinical utility of liquid biopsies in MM [ 25 , 50 ]. Further studies in larger patient cohorts that directly compare NGS- and MFC-approaches are needed to fully establish the preferred method for minimally invasive monitoring of MM.…”

Section: Discussionmentioning

confidence: 92%

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells

et al. 2022

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With the advent of novel, highly effective therapies for multiple myeloma (MM), classical serologic monitoring appears insufficient for response assessment and prediction of relapse. Moreover, serologic studies in MM are hampered by interference of therapeutic antibodies. The detection of malignant plasma cell clones by next generation sequencing (NGS) or multiparameter flow cytometry (MFC) circumvents these difficulties and can be performed in the peripheral blood (pB) by targeting circulating cell-free DNA (cfDNA) or circulating plasma cells (CPCs), thus also avoiding an invasive sampling procedure. Here, we applied NGS of VJ light chain (LC) rearrangements in cfDNA and MFC of magnetically-enriched CD138-positive CPCs (me-MFC) to investigate disease burden in unselected MM patients. Sequencing was successful for 114/130 (87.7%) cfDNA samples and me-MFC results were analyzable for 196/205 (95.6%) samples. MM clones were detectable in 38.9% of samples taken at initial diagnosis or relapse (ID/RD), but only in 11.8% of samples taken during complete remission (CR). Circulating MM plasma cells were present in 83.3% of ID/RD samples and 9.9% of CR samples. Residual disease assessment by NGS or me-MFC in samples taken during very good partial remission or CR was 80% concordant. Notably, 4/4 (NGS) and 5/8 (me-MFC) positive CR samples were from patients with oligo- or non-secretory myeloma. The time to progression was shorter if there was evidence of residual myeloma in the pB. Together, our findings indicate that our two novel analytical approaches accurately indicate the course of MM and may be particularly valuable for monitoring patients with serologically non-trackable disease.

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Section: Discussionmentioning

confidence: 92%

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells

et al. 2022

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“…First, the use of advanced minimal residual disease (MRD) testing using next-generation sequencing (NGS) technology with a minimum sensitivity of 1 in 10 5 nucleated cells is becoming more common place given studies suggesting this technology serves as an important prognostic factor [ 70 ]. While MRD testing via NGS is most commonly performed both at the end of induction therapy and post-auto-HSCT, the optimal timing of MRD testing in treating patients with relapsed MM remains a question [ 71 ]. Second, the sequencing of therapies in the relapsed MM patient population who have received an anti-BCMA targeting therapy (CAR-T therapies, belantamab-mafodotin) remains a debate.…”

Section: Discussionmentioning

confidence: 99%

Roadmap for new practitioners to navigate the multiple myeloma landscape

Tam

Smith

Allred

et al. 2022

Heliyon

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“…Improvements in MM therapy have led to more profound responses that are beyond the limit of detection for residual disease by monoclonal proteins in the serum and urine and conventional bone marrow examination. Therefore, more sensitive techniques for assessing residual disease, including the next-generation flow cytometry and NGS, have been developed ( 30 ). In Japan, next-generation flow cytometry is available in clinical practice ( 31 ).…”

Section: Areas Where Further Investigation Is Requiredmentioning

confidence: 99%

Recent advances in the management of older adults with newly diagnosed multiple myeloma in Japan

Suzuki

Maruyama

Iida

et al. 2022

Japanese Journal of Clinical Oncology

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Multiple myeloma is a cancer of plasma cells; the incidence rate of multiple myeloma is high among older adults. Although significant advances have been made in the clinical management of multiple myeloma driven by the introduction of novel drugs, such as proteasome inhibitors, immuno- modulators and antibodies, multiple myeloma remains incurable. Hence, the current therapeutic goal for multiple myeloma is to achieve long-term survival while maintaining a good quality of life. In this context, personalized treatment to balance the efficacy and safety of therapies is important, especially for older adults as they display diverse physical, cognitive or organ functioning. Furthermore, old age is also often associated with frailty. Several tools for evaluating frailty in older adults with multiple myeloma are now available, and frail patients defined by these tools have shown a poor prognosis and more treatment-related toxicities. In addition, it is important to evaluate other factors, such as the International Staging System, high-risk chromosomal abnormalities and treatment response, to predict the clinical course of patients. Further investigations are required to determine how these factors can optimize the treatment for multiple myeloma. In this review, we present a detailed account on the developments and issues related to the current treatment approaches for older adults with newly diagnosed multiple myeloma. We also discuss the ongoing phase III clinical study conducted by the lymphoma study group of the Japan Clinical Oncology Group, which targeted older adults with newly diagnosed multiple myeloma.

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Minimal residual disease in multiple myeloma: why, when, where

Cited by 13 publications

References 73 publications

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells

Roadmap for new practitioners to navigate the multiple myeloma landscape

Recent advances in the management of older adults with newly diagnosed multiple myeloma in Japan

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