The following criteria is provided for health care professionals.

Inclusion Criteria:

1. Subjects must have relapsed and/or refractory myeloma with measurable disease, as defined by at least one of the following: Serum monoclonal protein level >/=0.5 g/dL for Immunoglobulin G (IgG), Immunoglobulin A (IgA), or Immunoglobulin M (IgM) disease; Monoclonal protein or total serum Immunoglobulin D (IgD) >/=0.5 g/dL for IgD disease; Urinary Myeloma (M)-protein excretion of >/= 200 mg over a 24-hour period; Involved free light chain level >/=10 mg/dL, along with an abnormal free light chain ratio
2. Subjects must have had at least three lines of therapy for their disease, including a proteasome inhibitor and immunomodulatory drug (e.g., lenalidomide), with lines of therapy being separated by the presence of documented disease progression. Using this definition, treatment with induction therapy, followed by high dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period.
3. Subjects must have disease that has relapsed and/or refractory after their most recent therapy, with progressive disease (PD) being defined as an increase of 25% from the lowest response value in any one or more of the following: Serum M-component (the absolute increase must be >/=0.5 g/dL) and/or; Urine M-component (the absolute increase must be >/=200 mg/24 hours) and/or; Only in subjects without a measurable serum and urine M protein level: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase) must be >10 mg/dL; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder
4. Subjects with known polyneuropathy-organomegaly-endocrinopathy-M protein-skin lesions (POEMS) syndrome, and subjects with myeloma and amyloidosis will be eligible if they have measurable disease as defined above.
5. Subjects must have completed their most recent drug therapy directed at multiple myeloma in the following timeframes: Chemotherapy, biological therapy, immunotherapy, or an investigational therapy at least 2 weeks prior to starting DS3032b; Corticosteroids at least 2 weeks prior to starting DS3032b, except for a dose equivalent to dexamethasone of >/=4 mg/day; Nitrosoureas, nitrogen mustards, mitomycin C, or monoclonal antibodies at least 6 weeks prior to starting DS3032b; Autologous stem cell transplantation at least 12 weeks prior to starting DS3032b; Allogeneic stem cell transplantation at least 24 weeks prior to starting DS3032b, and these subjects must also NOT have moderate to severe active acute or chronic graft versus host disease (GVHD).
   1. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted if such therapy has not been changed within 8 weeks before study drug treatment.
6. Subjects >/= 18 years old
7. Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
8. Subjects must have evidence of adequate hepatic function, as defined by the following: aspartate aminotransferase (AST)/alanine transaminase (ALT) <3 x upper limit of normal (ULN); Bilirubin
9. Subjects must have evidence of adequate bone marrow reserves, as defined by the following: Absolute neutrophil count (ANC) >/=1,000 cells/mm^3 without growth factors within 1 week of the initiation of treatment; Hemoglobin >/=8 g/dL without red blood cell transfusions within 2 weeks of the initiation of treatment; Platelet count >/=70,000 cells/mm^3 if marrow plasmacytosis < 50%. Platelet count >/=30,000 cells/mm^3 if marrow plasmacytosis >/= 50%.
10. Subjects must have evidence of adequate renal function, as defined by the following: Serum creatinine within the institutional normal limits, OR if the creatinine is elevated: Creatinine clearance (CrCl) >/=30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula: i. Female CrCl=[(140 - age in years) x weight in kg x 0.85]/(72 x serum creatinine in mg/dL) ii. Male CrCl = [(140 - age in years) x weight in kg x 1.00]/(72 x serum creatinine in mg/dL)
11. Subjects must have adequate blood clotting function, defined as International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
12. Subjects must have evidence of adequate cardiac function, as defined by the following: Absence of New York Heart Association (NYHA) class II, III, or IV congestive heart failure Absence of uncontrolled angina or hypertension; Absence of myocardial infarction in the previous 6 months; Absence of clinically significant bradycardia, or other uncontrolled cardiac arrhythmia defined as grade 3 or 4 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
13. Subjects who have received radiation therapy targeting > 10% of the bone marrow space must have completed this at least 2 weeks prior to starting therapy with DS3032b.
14. Subjects who have undergone any recent major surgery must have done so at least 4 weeks prior to starting therapy with DS3032b, with the following exceptions: Vertebroplasty and/or kyphoplasty, which must have been performed at least 1 week prior to starting DS3032b; Planned elective surgery unrelated to the subject's diagnosis of multiple myeloma, such as hernia repair, may be allowed, at the discretion of the Principle Investigator, as long as it was performed at least 2 weeks prior to starting DS3032b, and subjects have recovered fully from this procedure
15. Subject must be able to provide written informed consent, comply with protocol visits and procedures, and take oral medication, and does not have any active infection or comorbidity that would interfere with therapy.
16. Subjects (male and female) of childbearing/reproductive potential must agree to use double barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug.
17. Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects).
18. Subjects must sign and date an Institutional Review Board-approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study-specific procedures or tests.
19. Subjects must be able and willing to provide bone marrow biopsies/aspirates as requested by the protocol.
20. Subjects must be willing to undergo malignancy genotyping for TP53 mutation, insertion, or deletion at screening.
21. Subjects must have an estimated life expectancy of at least 3 months.

Exclusion Criteria:

1. Subjects who are receiving any concurrent investigational or conventional agent with known or suspected activity against multiple myeloma, or those whose adverse events due to agents administered more than 4 weeks earlier have not recovered to a severity of grade 0 or grade 1. Subjects with chronic Grade 2 toxicities may be eligible per discretion of the Investigator and Sponsor (eg, Grade 2 chemotherapy-induced neuropathy).
2. Subject who received any therapies intended to treat malignancy within 21 days of first receipt of DS-3032b
3. Subjects with a malignancy that contains a non-synonymous mutation, insertion, or deletion in the TP53 gene determined previously or at screening.
4. Subjects with known central nervous system involvement with multiple myeloma will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
5. Subjects with a known history of allergic reactions attributed to compounds of similar chemical or biologic composition to DS3032b.
6. Subjects with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, in the opinion of the Principal Investigator.
7. Subjects who are pregnant or breast-feeding
8. Subjects with an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis A, B or C infection.
9. Subjects with gastrointestinal conditions that could affect the absorption of DS-3032b in the opinion of the Investigator.
10. Subjects with prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is >450 milliseconds (ms) for males and > 470 ms for females based on triplicate electrocardiogram (ECG).
11. Subjects who have required plasmapheresis and exchange less than 2 weeks prior to initiation of therapy with DS3032b.
12. Subjects with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Subjects are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years, and are considered by their physician to be at less than 30% risk of relapse. In addition, subjects with basal or squamous cell carcinoma of the skin, superficial carcinoma of the bladder, carcinoma of the prostate with a current prostate-specific antigen (PSA) value of <0.5 ng/mL, or cervical intraepithelial neoplasia will be eligible. Finally, subjects who are on hormonal therapy for a history of either prostate cancer or breast cancer may enroll, provided that there has been no evidence of disease progression during the previous three years.
13. Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
14. Subjects with prior treatment with an MDM2 inhibitor.
15. Nonclinical studies indicate that DS-3032b is metabolized by CYP3A4/5. Drugs that are strong inhibitors or inducers of these enzymes may alter the PK of DS-3032b and should therefore be avoided. St. John's wort (hypericin) therefore will not be permitted for 30 days before and during participation in the study. Because DS-3032b is a substrate for CYP3A4/5 and grapefruit juice is a CYP3A4/5 inhibitor, foods or beverages containing grapefruit should not be taken within 48 hours before initial dose of study drug and throughout the duration of the study.