OAB-059: Towards a comprehensive multimodal minimal residual disease assessment in multiple myeloma: the role of circulating cell-free DNA to define the extent of disease spreading

2021 ◽  
Vol 21 ◽  
pp. S37
Author(s):  
Marina Martello ◽  
Andrea Poletti ◽  
Enrica Borsi ◽  
Barbara Taurisano ◽  
Vincenza Solli ◽  
...  
Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Juan Du ◽  
Baoan Chen ◽  
Wanting Qiang ◽  
Yanchun Jia ◽  
Jing Lu ◽  
...  

Background: Minimal residual disease (MRD) is becoming standard diagnostic care for multiple myeloma. Here we investigate cell-free DNA chromosomal instability as minimal invasive biomarker for minimal residual disease monitoring. Methods: 55 patients were recruited, including 47 newly diagnosed and 8 relapsed multiple myelomas. Plasma samples were collected before treatments, end of 2 cycle and 4 cycle of treatments. Treatment response was assessed by using IMWG criteria. Cell-free DNA was analyzed by illumine HiSeq X10, followed by chromosomal instability analyses by a customized bioinformatics workflow, ultrasensitive chromosomal aneuploidy detector (UCAD), and cfDNA CIN responding to treatment was summarized as cfDNA MRD INDEX. Results: In this cohort study, 53 (96.3%) patients were found with treatment responses after 4 cycle of treatments, including 16 (29.1%) complete, 13 (23.6%) very good partial, 17 (30.9%) partial and 6 (10.9%) marginal responses. The other 2 (3.64%) recurrent MM experiences disease progression. At baseline, plasma cfDNA chromosomal aberrations were found in 14/17(82.3%) multiple myeloma patients. Less patients were found with detectable chromosomal changes after treatments (58.8% after C2, 41.2% after C4, versus 82.3% before treatments, P<0.01). The treatment responses identified in plasma cfDNA were summarized as cfDNA MRD INDEX. Low cfDNA MRD INDEX predicts better treatment responses (Fisher exact test, Odds ratio=7.3, P=4.69e-05). And it predicts complete response with sensitivity 100% and specificity 83.3%, with cutoff value 0.044. Furthermore, cfDNA CIN MRD index were found linearly correlated with percentage of malignant plasma cells from bone marrow aspiration as examined by flow cytometry assay (R-square=0.883, P<0.01). Cutoff -0.06 predicts 100% MRD negatives at specificity 100%. Conclusions: Plasma cfDNA CIN might be used for monitoring multiple myeloma patients treatment responses, especially for predicting minimal residual diseases. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 19 (10) ◽  
pp. e180
Author(s):  
Anjali Mookerjee ◽  
Meetu Dahiya ◽  
Ritu Gupta ◽  
Rakesh Kumar ◽  
Atul Sharma ◽  
...  

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3059-3068 ◽  
Author(s):  
Bruno Paiva ◽  
Jacques J. M. van Dongen ◽  
Alberto Orfao

Abstract Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as acute lymphoblastic leukemia. In multiple myeloma (MM), the majority of patients will inevitably relapse despite achievement of progressively higher complete remission (CR) rates. Novel treatment protocols with inclusion of antibodies and small molecules might well be able to further increase remission rates and potentially also cure rates. Therefore, MRD diagnostics becomes essential to assess treatment effectiveness. This review summarizes reports from the past 2 decades, which demonstrate that persistent MRD by multiparameter flow cytometry, polymerase chain reaction, next-generation sequencing, and positron emission tomography/computed tomography, predicts significantly inferior survival among CR patients. We describe the specific features of currently available techniques for MRD monitoring and outline the arguments favoring new criteria for response assessment that incorporate MRD levels. Extensive data indicate that MRD information can potentially be used as biomarker to evaluate the efficacy of different treatment strategies, help on treatment decisions, and act as surrogate for overall survival. The time has come to address within clinical trials the exact role of baseline risk factors and MRD monitoring for tailored therapy in MM, which implies systematic usage of highly sensitive, cost-effective, readily available, and standardized MRD techniques.


2012 ◽  
Vol 92 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Noemí Puig ◽  
María E. Sarasquete ◽  
Miguel Alcoceba ◽  
Ana Balanzategui ◽  
María C. Chillón ◽  
...  

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