# US 2023/0272484 A1 · Methods of prognosing, determining treatment course and treating multiple myeloma > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0272484 A1 - Document ID: US20230272484A1 - Status: Published application - Kind: A1 - Application number: 18/142,618 - Filed: 2023-05-03 - Published: 2023-08-31 - Earliest claimed: 2020-11-03 - Assignees: Yeda Research and Development Co. Ltd.; Ichilov Tech Ltd. - Applicants: Yeda Research and Development Co. Ltd.; Ichilov Tech Ltd. - Inventors: Ido AMIT; Assaf WEINER; Mor ZADA; Chamutal BORNSTEIN-OVITS; Shuang-Yin WANG; Yael COHEN - Web page: https://patentgrep.com/patent/US20230272484A1 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - A61K 31/69: Boron compounds - A61K 31/7076: containing purines, e.g. adenosine, adenylic acid - A61K 38/07: Tetrapeptides - A61K 38/13: Cyclosporins - A61P 35/00: Antineoplastic agents - 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 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A method of prognosing a subject diagnosed with multiple myeloma (MM) is provided. Also provided a method of treating a subject diagnosed with MM selected expressing intracellular PPIA and/or RRM2 above a predetermined threshold, the method comprising administering to the subject a therapeutically effective amount of at least one agent which specifically down-regulates activity or expression of PPIA and/or RRM2, thereby treating the subject. ## Claims ### Claim 1 A method of prognosing a subject diagnosed with multiple myeloma (MM), the method comprising determining in plasma cells (PC) of the subject a level of expression of at least one gene of Table A or A* and/or Table B or B*, wherein upregulation in at least one gene of Table A or A* and/or downregulation in at least one gens of Table B or B* as compared to expression of said genes in normal PC is indicative of poor prognosis, the method further comprising corroborating said prognosis with a Gold standard method. ### Claim 2 A method of determining responsiveness to treatment with Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (DARA-KRD) in a subject diagnosed with multiple myeloma (MM), the method comprising: treating the subject with Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (DARA-KRD); and determining in plasma cells (PC) of the subject a level of expression of at least one gens of Table C and/or Table D, wherein upregulation in at least one gene of Table C and/or downregulation in at least one gene of Table D as compared to expression of said at least one gene in normal PC is indicative of responsiveness to treatment with Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (DARA-KRD). ### Claim 3 (depends on 2) The method of claim 2, wherein said subject exhibits primary resistance to a first line treatment. ### Claim 4 (depends on 1) The method of claim 1, wherein said subject exhibits early relapse of less than 18 months following improvement. ### Claim 5 A method of treating a subject diagnosed with multiple myeloma (MM), the method comprising administering to the subject a therapeutically effective amount of a proteasome inhibitor and at least one agent which specifically down-regulates activity or expression of PPIA and/or RRM2, thereby treating the subject. ### Claim 6 A method of treating a subject diagnosed with MM selected expressing intracellular PPIA and/or RRM2 above a predetermined threshold, the method comprising administering to the subject a therapeutically effective amount of at least one agent which specifically down-regulates activity or expression of PPIA and/or RRM2, thereby treating the subject. ### Claim 7 (depends on 5) The method of claim 5, wherein the subject exhibits primary resistance to a first line treatment, or the subject is diagnosed with Relapsed/Refractory Multiple Myeloma (RRMM) or the subject exhibits upregulation of said intracellular PPIA and/or RRM2 as compared to expression of same in normal PC or said subject exhibits early relapse following an anti-MM treatment of less than 18 months. ### Claim 8 (depends on 5) The method of claim 5, wherein said proteasome inhibitor is selected from the group consisting of Carfilzomib, Bortezomib and Ixazomib. ### Claim 9 (depends on 5) The method of claim 5, further comprising determining a level of said intracellular PPIA and/or RRM2 in PC of the subject, wherein upregulation of said intracellular PPIA and/or RRM2 as compared to expression of same in normal PC is indicative of responsiveness to treatment with said proteasome inhibitor and said agent. ### Claim 10 (depends on 5) The method of claim 5, wherein said at least one agent is PPIA inhibitor. ### Claim 11 (depends on 5) The method of claim 5, wherein said PPIA inhibitor is cyclosporine A (CSa). ### Claim 12 (depends on 5) The method of claim 5, wherein said RRM2 inhibitor is Cladribine. ### Claim 13 (depends on 5) The method of claim 5, wherein said PPIA inhibitor is cyclosporine A (CSa) and said RRM2 inhibitor is Cladribine; or wherein said proteasome inhibitor is Carfilzomib, wherein said PPIA inhibitor is cyclosporine A (CsA) and optionally comprising dexamethasone. ### Claim 14 (depends on 6) The method of claim 6, wherein said proteasome inhibitor is selected from the group consisting of Carfilzomib, Bortezomib and Ixazomib. ### Claim 15 (depends on 6) The method of claim 6, further comprising determining a level of said intracellular PPIA and/or RRM2 in PC of the subject, wherein upregulation of said intracellular PPIA and/or RRM2 as compared to expression of same in normal PC is indicative of responsiveness to treatment with said proteasome inhibitor and said agent. ### Claim 16 (depends on 6) The method of claim 6, wherein said at least one agent is PPIA inhibitor. ### Claim 17 (depends on 6) The method of claim 6, wherein said PPIA inhibitor is cyclosporine A (CSa). ### Claim 18 (depends on 6) The method of claim 6, wherein said RRM2 inhibitor is Cladribine. ### Claim 19 (depends on 6) The method of claim 6, wherein said PPIA inhibitor is cyclosporine A (CSa) and said RRM2 inhibitor is Cladribine; or wherein said proteasome inhibitor is Carfilzomib, wherein said PPIA inhibitor is cyclosporine A (CsA) and optionally comprising dexamethasone.