Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT

Inclusion Criteria:

1. Age 20\~70
2. Progressive disease after 1st ASCT
3. Duration of response after 1st ASCT \> 12 months
4. Measurable disease (+)

   * Serum M-protein ≥ 1 g/dL
   * Urine M-protein ≥ 200 mg/24 hr
   * Serum Free Light Chain(FLC) assay: involved FLC level ≥10 mg/dL (serum Free Light Chain ratio is abnormal)
5. Adequate organ function for induction \& ASCT

   * 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 bone marrow)
   * Hemoglobin ≥ 8.0 g/dL
   * Creatinine clearance ≥ 30 mL/minute
   * Serum Bilirubin ≤ 1.5 x upper limit of normal
   * Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) ≤ 3 x upper limit of normal
6. Eastern Cooperative Oncology Group performance scale 0\~2
7. Survival expectancy \> 3 months
8. Adequately controlled hepatitis B(HBV) \& hepatitis C(HCV)
9. Written informed consent
10. Optimal contraceptions

Exclusion Criteria:

1. Prior refractoriness or intolerance to carfilzomib
2. Prior refractoriness or intolerance to lenalidomide/dexamethasone
3. Any treatment after progressive disease after 1st ASCT. High-dose dexamethasone or palliative radiation is permitted.
4. Waldenstroem's macroglobulinemia, POEMS syndrome, or plasma cell leukemia
5. Pregnant or nursing lactating women
6. Myocardial infarct within 6 months, heart failure of New York Heart Association(NYHA) Class III\~IV, uncontrolled ventricular arrhythmia, severe coronary arterial obstructive disease
7. Uncontrolled hypertension (Defined as an average systolic blood pressure \>= 160 mmHg or diastolic \>= 100 mmHg) or diabetes
8. Grade 3\~4 neuropathy
9. HIV infection
10. Severe or uncontrolled medical conditions, laboratory abnormalities, or psychiatric disorders that may preclude the participation of the study by the physician's discretion
11. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
12. Diagnosis of other malignant disease other than myeloma within 5 year. Exceptions are properly treated non-melanomatous skin cancers, cervical intraepithelial neoplasia, prostate cancer that do not require treatment, or properly excised well-differentiated thyroid cancers