Phase II Study of Carfilzomib, Pomalidomide, and Dexamethasone for Myeloma Patients Who Had Relapsed or Progressed After Carfilzomib, Lenalidomide, and Dexamethasone

Inclusion Criteria:

1. Age from 20 to 80 years-old
2. Relapse or progression of multiple myeloma after treatment ofcarfilzomib/lenalidomide/dexamethasone (KRd)
3. KRd treatment 12 cycles or more and lenalidomide maintenance for at least 6 months orKRd 4-6 cycles followed by ASCT and lenalidomide maintenance for at least 6 months
4. Measurable disease

• Serum M-protein ≥ 1 g/dL (10 g/L)
• Urine M-protein ≥ 200 mg/24 hr
• Serum FLC assay: difference of FLC ≥ 10 mg/dL (100 mg/L) provided serum FLC ratiois abnormal (KL ratio < 0.26 or > 1.65) if Serum EP or urine EP is not measurable

5. Adequate organ functions

• Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
• Platelets ≥ 50 x 109/L (≥ 30 x 109/L if myeloma involvement is > 50% in the bonemarrow)
• Hemoglobin ≥ 8.0 g/dL
• Creatinine clearance ≥ 30 mL/minute or Serum Cr <3.0 g/dL
• Serum Bilirubin ≤ 1.5 x ULN
• AST and ALT ≤ 3 x ULN

6. Eastern Cooperative Oncology Group performance scale 0~2
7. Life expectancy longer than 3 months
8. Written informed consent
9. Prior therapy with bortezomib
10. Patients who meet the following criteria

• If a woman of childbearing age
• Women who are willing to use two reliable methods of contraception from 4weeks prior to administration of study drug, while receiving, temporarilysuspending administration, and 4 weeks after administration of the studydrug.
• Women who have a negative pregnancy test with a minimum sensitivity of 25IU/mL under medical management
• For men Men who agree to abstain from absolute abstinence or use a proper methodof contraception for the entire duration of treatment and 28 days after the lastdose
• Women of childbearing age Women who have not undergone hysterectomy orbilateral oophorectomy, women who have not undergone spontaneous menopausefor at least 24 consecutive months (i.e., menstruate at any time during thelast 24 months. However, amenorrhea after chemotherapy does not exclude thepossibility of pregnancy).
• Proper method of contraception
• Very effective way Intrauterine device, hormone therapy (hormone implant,intrauterine system releasing levonorgestrel, medroxyprogesterone acetate depotinjection, tablets containing progesterone to inhibit ovulation), tubal ligation,varicose veins in men
• Effective way Men's condom use, diaphragm method, cervical cap

Exclusion Criteria:

1. Grade 3~4 non-hematologic toxicity by carfilzomib during the previous carfilzomibtreatment
2. Prior therapy with pomalidomide
3. Hypersensitivity to thalidomide or lenalidomide
4. Previous refractoriness to carfilzomib according to the IMWG criteria
5. Myocardial infarct within 6 months, heart failure of NYHA Class III~IV, uncontrolledventricular arrhythmia, severe coronary arterial obstructive disease
6. Active infection with 14 days prior to treatment
7. Uncontrolled hypertension (Defined as an average systolic blood pressure >= 160 mmHgor diastolic >= 100 mmHg) or diabetes (HbA1c > 7.0%)
8. HIV, HBV, HCV infection (exception if adequately controlled HBV (undetectable HBV DNA (< 20 IU/mL or concurrent use of an anti-viral agent), HCV)
9. Severe or uncontrolled medical conditions, laboratory abnormalities, or psychiatricdisorders that may preclude the participation of the study by the physician'sdiscretion
10. Contraindication to any of the required concomitant drugs or supportive treatments,including hypersensitivity to all anticoagulation and antiplatelet options, antiviraldrugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
11. Diagnosis of other malignant disease other than myeloma within 5 year. Exceptions areproperly treated non-melanomatous skin cancers, cervical intraepithelial neoplasia,prostate cancer that do not require treatment, or properly excised well-differentiatedthyroid cancers.
12. Pregnant or nursing women
13. Waldenstroem's macroglobulinemia, POEMS syndrome, or plasma cell leukemia, light chainamyloidosis
14. LV ejection fraction < 40%