Pilot Study Using Changes in Serum BCMA to Determine Disease Progression in Multiple Myeloma

Inclusion Criteria: * Subjects must meet all the following inclusion criteria to be eligible to enroll in this study. 1. Has a diagnosis of MM based on standard criteria as follows: Major criteria: <!-- --> 1. Plasmacytomas on tissue biopsy 2. BM plasmacytosis (greater than 30% plasma cells) 3. Monoclonal immunoglobulin spike on serum electrophoresis IgG greater than 3.5 g/dL or IgA greater than 2.0 g/dL or kappa or lambda light chain excretion greater than 1 g/day on 24-hour urine protein electrophoresis Minor criteria: <!-- --> 1. BM plasmacytosis (10% to 30% plasma cells) 2. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria 3. Lytic bone lesions 4. Normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL Any of the following sets of criteria will confirm the diagnosis of multiple myeloma: * any 2 of the major criteria * major criterion 1 plus minor criterion 2, 3, or 4 * major criterion 3 plus minor criterion 1 or 3 * minor criteria 1, 2, and 3, or 1, 2, and 4 2\. Currently has MM with measurable disease, defined as: * a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or urine monoclonal protein levels of at least 200 mg/24 hours * for patients without measurable serum and urine M-protein levels, an involved SFLC \> 100 mg/L or abnormal SFLC ratio * for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 5500 mg/L or meet other measurable disease eligibility criteria 3\. Currently has progressive MM and has received at least 2 prior regimens including lenalidomide, a proteasome inhibitor, and an anti-CD38 antibody: * Patients are considered relapsed when they progress greater than 8 weeks from their last dose of treatment * Patients are refractory when they progress while currently receiving the treatment or within 8 weeks of its last dose 4\. Ruxolitinib naïve 5\. Understand and voluntarily sign an informed consent form before receiving any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn at any time without prejudice to their future medical care 6\. Able to adhere to the study visit schedule and other protocol requirements 7\. ECOG performance status of ≤ 2 at study entry 8\. Life-expectancy of greater than 3 months 9\. Laboratory test results within these ranges at Screening and confirmed at enrollment prior to drug dosing on Cycle 1, Day 1: * Absolute neutrophil count ≥ 1.5 x 109/L o If the bone marrow is extensively infiltrated (≥ 70% plasma cells) then ≥ 1.0 x 109/L * Platelet count ≥ 75 x 109/L o Patients must not have received platelet transfusion for at least 7 days prior to receiving screening platelet count * If the bone marrow is extensively infiltrated (≥ 70% plasma cells) then ≥ 50 x 109/L * If patient have creatinine clearance of less than 60mL/min, patient's platelet count must be greater than 150 x 109/L * Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment o Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin. * Calculated or measured CrCl \> 60 mL/minute per Cockcroft-Gault (Appendix 3) * Total bilirubin levels ≤ 2.0 mg/dL * AST (SGOT) and ALT (SGPT) ≤ 2 x ULN * Serum potassium 3.0 - 5.5 mEq/L 10\. Patients receiving lenalidomide (Part 2 of the study) must be registered into the mandatory REVLIMID REMS™ program, and be willing and able to comply with the requirements of the REVLIMID REMS™ program 11\. FCBP† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting ruxolitinib + methylprednisolone and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking ruxolitinib with or without lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. †A FCBP (female of childbearing potential) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; and 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) 12\. Able to take antiplatelet therapy if platelet count is above 30 x 109/L. Options include aspirin (acetylsalicylic acid, ASA) at 81 or 325 mg/daily and warfarin or low molecular weight heparin if ASA-intolerant Exclusion Criteria: * Subjects meeting any of the following exclusion criteria are not to be enrolled in the study: 1. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Plasma cell leukemia (\> 2.0 × 109/L circulating plasma cells by standard differential) 3. Primary amyloidosis 4. Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas 5. Patients with uncontrolled infections 6. Impaired cardiac function or clinically significant cardiac diseases, incl