scholarly journals Liquid biopsies for multiple myeloma in a time of precision medicine

2020 ◽  
Vol 98 (4) ◽  
pp. 513-525 ◽  
Author(s):  
Bruna Ferreira ◽  
Joana Caetano ◽  
Filipa Barahona ◽  
Raquel Lopes ◽  
Emilie Carneiro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine ◽  
Liquid Biopsies

Single-cell profiling of tumour evolution in multiple myeloma — opportunities for precision medicine

2022 ◽  
Author(s):  
Ankit K. Dutta ◽  
Jean-Baptiste Alberge ◽  
Romanos Sklavenitis-Pistofidis ◽  
Elizabeth D. Lightbody ◽  
Gad Getz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine ◽  
Single Cell ◽  
Single Cell Profiling

scholarly journals Experimental treatment of multiple myeloma in the era of precision medicine

2016 ◽  
Vol 1 (1) ◽  
pp. 37-51 ◽  
Author(s):  
Maria Teresa Di Martino ◽  
Mariamena Arbitrio ◽  
Pietro Hiram Guzzi ◽  
Mario Cannataro ◽  
Pierosandro Tagliaferri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine ◽  
Experimental Treatment

scholarly journals Liquid Biopsies in Multiple Myeloma

Liquid Biopsy ◽  
2019 ◽  
Author(s):  
David Vrabel ◽  
Adela Souckova ◽  
Lenka Sedlarikova ◽  
Sabina Sevcikova
Keyword(s):  
Multiple Myeloma ◽  
Liquid Biopsies

scholarly journals Integrated phosphoproteomics and transcriptional classifiers reveal hidden RAS signaling dynamics in multiple myeloma

2019 ◽  
Vol 3 (21) ◽  
pp. 3214-3227 ◽  
Author(s):  
Yu-Hsiu T. Lin ◽  
Gregory P. Way ◽  
Benjamin G. Barwick ◽  
Margarette C. Mariano ◽  
Makeba Marcoulis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine ◽  
Mapk Signaling ◽  
Ras Signaling ◽  
Kras Mutations ◽  
Signaling Dynamics ◽  
Key Points

Key Points NRAS and KRAS mutations lead to different downstream transcriptional signatures and patient prognoses under current myeloma therapies. RAS genotype alone does not strongly predict degree of active MAPK signaling, suggesting alternate precision medicine approaches are needed.

scholarly journals “Direct to Drug” screening as a precision medicine tool in multiple myeloma

2020 ◽  
Vol 10 (5) ◽  
Author(s):  
Cecilia Bonolo de Campos ◽  
Nathalie Meurice ◽  
Joachim L. Petit ◽  
Alysia N. Polito ◽  
Yuan Xiao Zhu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine ◽  
Drug Screening

scholarly journals A Next Generation Liquid Biopsy Approach for Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-33
Author(s):  
Daniel Auclair ◽  
Mark Bustoros, MD ◽  
Carrie Cibulskis ◽  
Teni Dowdell ◽  
Svetlana Gavrilov ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Molecular Characterization ◽  
Liquid Biopsy ◽  
Clinical Care ◽  
Buffy Coat ◽  
Gene Panel ◽  
Clinical Grade ◽  
Liquid Biopsies ◽  
Validation Data ◽  
Gene Assay

Direct-to-Patient (DTP) Multiple Myeloma (MM) research studies have been launched recently, including PCROWD (NCT02269592), PROMISE (NCT03689595) and the MMRF CureCloud Research Initiative (NCT03657251), aimed at enrolling thousands of individuals from whom comprehensive molecular and immune analyses will be generated from blood specimens and the resulting data aggregated with the correlating clinical information. To support the molecular characterization of liquid biopsies for such DTP efforts, a set of myeloma-specific liquid biopsy approaches were developed. First, a hybrid selection panel was developed that detects somatic variants present in a patient's circulating-free DNA (cfDNA) in 70 commonly altered MM and Clonal Hematopoiesis of Indeterminate Potential (CHIP) genes. For this MM 70-Gene cfDNA Assay, samples are received as blood in a StreckTM tube designed for stabilization of cfDNA and DNA is extracted from buffy coat using magnetic bead-based chemistry. Deep coverage sequencing (80,000x depth) is performed and duplex BAM files generated with UMI alignment and error correction allowing for sensitive detection of clinically relevant variants. Technical validation data on healthy donor cfDNA mixes was generated using samples with a range of cfDNA inputs. This data determined that the assay is capable of achieving >90% sensitivity for detecting somatic events present at 1% variant allele frequency with a specificity of <0.2 false positives per megabase. Using a clinical cohort, we observed a strong correlation between Bone Marrow Aspirate (BMA) and cfDNA samples with the vast majority of variants previously detected in BMA also identified via the MM-70 Gene panel analysis. Interestingly, we also saw evidence of additional somatic variants identified in cfDNA previously undetected in BMA analysis. Because one the aims of this effort is to return results to treating physicians, a clinical-grade (CLIA) pipeline was established. For that CLIA pipeline, the variants reported are a subset of all the events detected by the MM 70-Gene Assay. The events detected in the assay are reviewed by experienced molecular pathologists at the Dana Farber Cancer Institute (DFCI) who have developed a customized reporting process. These reports utilize an internally-developed knowledgebase of variant/gene annotations that leverages the DFCI expertise in hematologic malignancies and myeloma specifically. The reports are then provided back through providers to the patient via the CureCloud system for their use in clinical care and trial identification. In order to complement the MM-70 Gene panel with copy number and translocation information, we have been exploring Circulating Multiple Myeloma Cells (CMMCs). Our current approach involves automated capture of CMMCs using ferrofluids coated with MM-selective and discriminating antibodies to immunomagnetically enrich circulating plasma cells. The highly enriched CMMCs fractions generated in such a fashion are then submitted for molecular characterization. At the submission date of this abstract, 163 patients have been fully enrolled into CureCloud from which results will be presented. In summary, we have developed a robust and very sensitive clinical-grade next-gen liquid biopsy sequencing platform allowing for minimally invasive monitoring of MM disease genomics that can be used to complement other more classical approaches and to help support our Direct-To-Patient Initiatives. Especially in this post-COVID19 era, such liquid biopsy-based approaches that avoid clinic visits for the patients and can be performed through at-home mobile phlebotomy are emerging as important new options. Disclosures Kim: LabCorp: Consultancy; Quanterix, Inc: Consultancy; PapGene, Inc: Consultancy. Ghobrial:AbbVie: Consultancy; GNS Healthcare: Consultancy; GlaxoSmithKline: Consultancy; Genentech: Consultancy; Noxxon Pharma: Consultancy; Novartis: Consultancy; Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Cellectar: Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.

scholarly journals Precision medicine in multiple myeloma: are we there yet?

2019 ◽  
Vol 4 (2) ◽  
pp. 51-53 ◽  
Author(s):  
Daniel Auclair ◽  
Sagar Lonial ◽  
Kenneth C. Anderson ◽  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine

scholarly journals Precision Medicine for Relapsed Multiple Myeloma on the Basis of an Integrative Multiomics Approach

2018 ◽  
pp. 1-17 ◽  
Author(s):  
Alessandro Laganà ◽  
Itai Beno ◽  
David Melnekoff ◽  
Violetta Leshchenko ◽  
Deepu Madduri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine ◽  
Rna Sequencing ◽  
Plasma Cells ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Precision Oncology ◽  
Dna Mutation ◽  
Dna And Rna ◽  
Disease Marker

Purpose Multiple myeloma (MM) is a malignancy of plasma cells, with a median survival of 6 years. Despite recent therapeutic advancements, relapse remains mostly inevitable, and the disease is fatal in the majority of patients. A major challenge in the treatment of patients with relapsed MM is the timely identification of treatment options in a personalized manner. Current approaches in precision oncology aim at matching specific DNA mutations to drugs, but incorporation of genome-wide RNA profiles has not yet been clinically assessed. Methods We have developed a novel computational platform for precision medicine of relapsed and/or refractory MM on the basis of DNA and RNA sequencing. Our approach expands on the traditional DNA-based approaches by integrating somatic mutations and copy number alterations with RNA-based drug repurposing and pathway analysis. We tested our approach in a pilot precision medicine clinical trial with 64 patients with relapsed and/or refractory MM. Results We generated treatment recommendations in 63 of 64 patients. Twenty-six patients had treatment implemented, and 21 were assessable. Of these, 11 received a drug that was based on RNA findings, eight received a drug that was based on DNA, and two received a drug that was based on both RNA and DNA. Sixteen of the 21 evaluable patients had a clinical response (ie, reduction of disease marker ≥ 25%), giving a clinical benefit rate of 76% and an overall response rate of 66%, with five patients having ongoing responses at the end of the trial. The median duration of response was 131 days. Conclusion Our results show that a comprehensive sequencing approach can identify viable options in patients with relapsed and/or refractory myeloma, and they represent proof of principle of how RNA sequencing can contribute beyond DNA mutation analysis to the development of a reliable drug recommendation tool.

The treatment of multiple myeloma in an era of precision medicine

2019 ◽  
Vol 4 (3) ◽  
pp. 153-162 ◽  
Author(s):  
Nicolas Kint ◽  
Sophie Vlayen ◽  
Michel Delforge
Keyword(s):  
Multiple Myeloma ◽  
Precision Medicine
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