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Laganà A, Beno I, Melnekoff D, et al. Precision Medicine for Relapsed Multiple Myeloma on the Basis of an Integrative Multiomics Approach. JCO Precis Oncol. 2018;2018doi: 10.1200/PO.18.00019.
Laganà, A., Beno, I., Melnekoff, D., Leshchenko, V., Madduri, D., Ramdas, D., Sanchez, L., Niglio, S., Perumal, D., Kidd, B. A., Miotto, R., Shaknovich, R., Chari, A., Cho, H. J., Barlogie, B., Jagannath, S., Dudley, J. T., & Parekh, S. (2018). Precision Medicine for Relapsed Multiple Myeloma on the Basis of an Integrative Multiomics Approach. JCO precision oncology, 2018. https://doi.org/10.1200/PO.18.00019
Laganà, Alessandro, et al. "Precision Medicine for Relapsed Multiple Myeloma on the Basis of an Integrative Multiomics Approach." JCO precision oncology vol. 2018 (2018). doi: https://doi.org/10.1200/PO.18.00019
Laganà A, Beno I, Melnekoff D, Leshchenko V, Madduri D, Ramdas D, Sanchez L, Niglio S, Perumal D, Kidd BA, Miotto R, Shaknovich R, Chari A, Cho HJ, Barlogie B, Jagannath S, Dudley JT, Parekh S. Precision Medicine for Relapsed Multiple Myeloma on the Basis of an Integrative Multiomics Approach. JCO Precis Oncol. 2018;2018. doi: 10.1200/PO.18.00019. Epub 2018 Aug 08. PMID: 30706044; PMCID: PMC6350920.
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JCO Precis Oncol. 2018;2018. doi: 10.1200/PO.18.00019. Epub 2018 Aug 08.

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

JCO precision oncology

Alessandro Laganà, Itai Beno, David Melnekoff, Violetta Leshchenko, Deepu Madduri, Dennis Ramdas, Larysa Sanchez, Scot Niglio, Deepak Perumal, Brian A Kidd, Riccardo Miotto, Rita Shaknovich, Ajai Chari, Hearn Jay Cho, Bart Barlogie, Sundar Jagannath, Joel T Dudley, Samir Parekh

Affiliations

  1. , and , Icahn School of Medicine at Mount Sinai, New York, NY; and , Cancer Genetics, Rutherford, NJ.

PMID: 30706044 PMCID: PMC6350920 DOI: 10.1200/PO.18.00019

Abstract

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.

Conflict of interest statement

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationsh

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