# US 2020/0399709 A1 · Methods for the in vitro determination of the outcome and for the treatment of individuals having multiple myeloma

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- Number: US 2020/0399709 A1
- Document ID: US20200399709A1
- Status: Published application
- Kind: A1
- Application number: 16/968,448
- Filed: 2019-02-07
- Published: 2020-12-24
- Earliest claimed: 2018-02-08
- Assignees: Centre National De La Recherche Scientifique; Universite De Montpellier; Centre Hospitalier Et Universitaire De Montpellier
- Applicants: Centre National De La Recherche Scientifique; Universite De Montpellier; Centre Hospitalier Et Universitaire De Montpellier
- Inventors: Alboukadel KASSAMBARA; Jérôme MOREAUX; Wafa HASSEN
- Web page: https://patentgrep.com/patent/US20200399709A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation
- G16B 40/00: ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16H 10/40: for data related to laboratory analysis, e.g. patient specimen analysis
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA

## Abstract

Disclosed is a method for in vitro predicting the outcome of an individual having a multiple myeloma, including: -a) measuring the expression level of at least 2 genes encoding a ROS detoxifying (AOX) protein selected in a group including AKR1 B1, ARNT, CAT, CBR DHCR24, EGLN1, GLRX2, HIF1A, MGST1, MSRB1, PRDX6, SLC7A1 1, SOD1, SRXN1, TALDO1 and TXN and/or the expression level of at least 2 genes encoding ROS producing (ROS) protein selected in a group including CYBA, CYB5A, CYC1, NCF1 B, NCF1 C, NCF4, NDUFA12, NDUFS2, NDUFS8, SHC1 and UQCR10, in a biological sample obtained from the individual; -b) calculating an AOX score value and/or a ROS score value from the respective expression level(s) obtained at step a); -c) classifying the individual as having a good prognosis status or a bad prognosis status, by comparing the score value obtained at step b) with a reference score value.

## Claims

### Claim 1

A method for treating an individual having a multiple myeloma, able to respond to a therapeutic anti-multiple myeloma (anti-MM) treatment, comprising the steps of:
a) identifying the individual able to respond to the therapeutic anti-MM treatment by performing the following steps:
i) measuring the expression level of at least 2 genes encoding a ROS detoxifying (AOX) protein selected in a group comprising AKR1B1, ARNT, CAT, CBR1, DHCR24, EGLN1, GLRX2, HIF1A, MGST1, MSRB1, PRDX6, SLC7A11, SOD1, SRXN1, TALDO1 and TXN and/or the expression level of at least 2 genes encoding ROS producing (ROS) protein selected in a group comprising CYBA, CYB5A, CYC1, NCF1B, NCF1C, NCF4, NDUFA12, NDUFS2, NDUFS8, SHC1 and UQCR10, in a biological sample obtained from said individual;
ii) calculating an AOX score value and/or a ROS score value from the said respective expression level obtained at step a);
iii) comparing said AOX score value and/or said ROS score value to a respective predetermined reference value,
iv) confirming that said AOX score value and/or said ROS score value is lower than the respective predetermined reference value and concluding that said individual is able to respond to said therapeutic anti-MM treatment,
b) administering to said individual an effective amount of said therapeutic anti-MM treatment.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The method according to claim 1, wherein the expression level of 16 genes encoding a ROS detoxifying (AOX) protein consisting of AKR1B1, ARNT, CAT, CBR1, DHCR24, EGLN1, GLRX2, HIF1A, MGST1, MSRB1, PRDX6, SLC7A11, SOD1, SRXN1, TALDO1 and TXN, and/or the expression level of 11 genes encoding ROS producing (ROS) protein consisting of CYBA, CYB5A, CYC1, NCF4, NCF1B, NCF1C, NDUFA12, NDUFS2, NDUFS8, SHC1 and UQCR10, is measured at step a).

### Claim 4 (depends on 1)

The method according to claim 1, wherein the expression level of 16 genes encoding a ROS detoxifying (AOX) protein consisting of AKR1B1, ARNT, CAT, CBR1, DHCR24, EGLN1, GLRX2, HIF1A, MGST1, MSRB1, PRDX6, SLC7A11, SOD1, SRXN1, TALDO1 and TXN, and the expression level of 11 genes encoding ROS producing (ROS) protein consisting of CYBA, CYB5A, CYC1, NCF4, NCF1B, NCF1C, NDUFA12, NDUFS2, NDUFS8, SHC1 and UQCR10, is measured at step WI).

### Claim at position 5

5-9. (canceled)

### Claim 10 (depends on 1)

The method according to claim 1, wherein the therapeutic anti-MM treatment comprises at least one anticancer compound, at least one bisphosphonate, radiation, surgery, stem cell transplant, plasmapheresis and a combination thereof.

### Claim at position 7

11-18. (canceled)

### Claim 19 (depends on 10)

The method according to claim 10, wherein the anticancer compound is selected from a group consisting of adriamycin, etoposide, cis-platin, arabinosyl cytosine, thalidomide, bendamustine, bortezomib, carfilzomib, cyclophosphamide, daratumumab, dexamethasone, doxorubicin, elotuzumab, etoposide, ixazomib, liposomal doxorubicin, melphalan, panobinostat, prednisone, vincristine and combinations thereof.

### Claim 20 (depends on 19)

The method according to claim 19, wherein the anticancer compound is selected from a group consisting of bendamustine, bortezomib, carfilzomib, cyclophosphamide, daratumumab, dexamethasone, doxorubicin, elotuzumab, etoposide, ixazomib, liposomal doxorubicin, melphalan, panobinostat, prednisone, vincristine and combinations thereof.

### Claim 21 (depends on 20)

The method according to claim 20, wherein the anticancer compound is selected from a group consisting of bortezomib and melphalan.
