MTD, Safety, and Efficacy of Pomalidomide (CC-4047) Alone or With Low-dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma

The Phase 1 segment of the study was designed to determine the maximum tolerated dose (MTD)
of single-agent pomalidomide, which was to be determined in the first cycle of treatment.
Following completion of the first cycle, participants were allowed to continue the study at
their assigned dose of pomalidomide.

Participants who developed progressive disease (PD) at any time, or who had not achieved at
least a 25% reduction of serum myeloma (M)-protein levels (if measurable) and a 50%
reduction of urine M-protein (if measurable) compared with baseline after completion of 4
cycles of pomalidomide, had the option to receive oral dexamethasone 40 mg on days 1, 8, 15,
and 22 of each 28-day treatment cycle in addition to their current dose of pomalidomide.
Participants with PD who chose not to add dexamethasone to pomalidomide therapy were to be
discontinued from the study. Participants who chose to add dexamethasone were allowed to
continue study treatment until PD developed again, unacceptable toxicity or participant
withdrew consent, at which time they were to be discontinued.

Based on results from the phase 1 portion, the Data Monitoring Committee confirmed 4 mg/day
as MTD of pomalidomide. Therefore, the recommended starting dose of pomalidomide for Phase 2
was 4 mg/day on Days 1-21 of each 28-day cycle. In the combination treatment arm, the
starting dose of dexamethasone was 40 mg once per day. For subjects who were > 75 years of
age, the starting dose of dexamethasone was 20 mg once per day. To prevent blood clots, all
participants were to be given aspirin 81-100 mg daily (commercial supply) unless
contraindicated. If contraindicated, another form of anti-thrombotic therapy was provided.

Participants in the Phase II combination treatment arm could continue study treatment until
PD developed, at which time they were to be discontinued. Participants in the single agent
pomalidomide treatment arm who developed PD, confirmed by the IRAC, at any time had the
option to receive oral dexamethasone in addition to their current dose of pomalidomide at
the starting dose described above. Participants with PD who chose not to add dexamethasone
to pomalidomide therapy were discontinued from study treatment. Participants who chose to
add dexamethasone to pomalidomide therapy could continue study treatment until PD developed
again, unacceptable toxicity or participant withdrew consent, at which point they were
discontinued.

Upon discontinuation from study treatment for PD or any other reason, participants were to
be assessed two times per year, up to five years, for survival, second primary malignancy
and subsequent anti-myeloma therapies.

Two analyses were planned during the course of the Phase 2 segment: one interim analysis (at
50% information of progression-free survival (PFS) events) and one final analysis. The Data
Monitoring Commmittee recommended that Celgene personnel be unblinded based on the strength
of the data. Subsequently, Celgene decided to file an application based on more current
study data. The product was approved by the FDA in February 2013.

Since no further analyses are required per protocol nor to support the marketing
application, the study was amended to remove undue burden from patients who remain on active
treatment by ending the treatment segments of this study and transferring all active
patients tothe Long-term Follow-up Phase. These patients who continue to be treated with
pomalidomide will be provided Pomalyst through the Celgene Patient Support Program (Pomalyst
REMSTM) until disease progression, unacceptable toxicity, the investigator decides to change
therapy or patient decision. Investigators will treat their patients according to the local
standard of care and follow the assessments required for patients in the Long-term Follow-up
Phase. These assessments include subsequent myeloma therapies, second primary malignancies
and survival.

The study continues. A final analysis will be performed when the study is completed and
results reported as available.

Inclusion Criteria:

- Must be greater than or equal to 18 years at the time of signing the informed consent
form

- Must be able to adhere to the study visit schedule and other protocol requirements

- Have a documented diagnosis of multiple myeloma and have relapsed and refractory
disease. Patients must have received at least 2 prior therapies. Patients must have
relapsed after having achieved at least stable disease for at least one cycle of
treatment to at least one prior regimen and then developed PD. Patients must also
have documented evidence of PD during or within 60 days (measured from the end of the
last cycle) of completing treatment with the last anti-myeloma drug regimen used just
prior to study entry (refractory disease)

- Patients must have also undergone prior treatment with at least 2 cycles of
lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or
within the same regimen)

- Measurable levels of myeloma paraprotein in serum (greater than or equal to 0.5 g/dL)
or urine (greater than or equal 0.2 g/dL excreted in a 24 hour collection sample)

- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

- Females of childbearing potential (FCBP) [An FCBP is a sexually mature woman who: 1)
has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses
at any time in the preceding 24 consecutive months)] must agree to refrain from
becoming pregnant for 28 days prior to initiation of study drug, while on study drug
and for 28 days after discontinuation of study drug and must agree to regular
pregnancy testing during this timeframe.

- All patients must also agree to refrain from donating blood while on study drug and
for 28 days after discontinuation from this study

- Males must agree to use a latex condom during any sexual contact with FCBP while
participating in the study and for 28 days following discontinuation from this study
even if he has undergone a successful vasectomy. Males must also agree to refrain
from donating blood, semen or sperm during the above referenced timeframe.

- All patients must agree not to share medication with another person.

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the patient from signing the informed consent form.

- Any serious concurrent medical conditions that may make the patient non-evaluable or
put the patient's safety at risk.

- Pregnant or lactating females

- Any of the following laboratory abnormalities:

- Absolute neutrophil count (ANC) < 1,000 cells/mm3

- Platelet count < 75,000/mm3 for patients in whom < 50% of bone marrow nucleated
cells are plasma cells; or a platelet count < 30,000/mm3 for patients in whom ≥
50% of bone marrow nucleated cells are plasma cells

- Serum creatinine > 3.0 mg/dL

- Serum glutamic oxaloacetic transaminase/Aspartate transaminase (SGOT/AST) or
Serum Glutamic Pyruvate Transaminase/Alanine transaminase (SGPT/ALT) > 3.0 X
upper limit of normal (ULN)

- Serum total bilirubin > 2.0 mg/dL

- Prior history of malignancies, other than multiple myeloma, unless the patient has
been free of the disease for ≥ 3 years. Exceptions include the following:

- Basal or squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix or breast

- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

- Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C
Virus (HCV) infection

- Hypersensitivity to thalidomide, lenalidomide, or dexamethasone

- Peripheral neuropathy ≥ Grade 2

- Use of any anti-myeloma drug therapy within 14 days of the initiation of study drug
treatment or use of any experimental non-drug therapy within 28 days of the
initiation of study drug treatment

- Radiation therapy within 14 days of initiation of study drug treatment Inability or
unwillingness to comply with birth control requirements