Methods of prognosing, determining treatment course and treating multiple myeloma

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).

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.

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.