REVLIMID® (lenalidomide) is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1–risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

REVLIMID is only available through a restricted distribution program, REVLIMID REMS®.

CAN YOU CUT TRANSFUSION DEPENDENCE OUT OF DEL 5Q MDS?

Please see full Prescribing Information, including Boxed WARNINGS, and Important Safety Information throughout presentation.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program, the REVLIMID REMS® program.

Information about the REVLIMID REMS® program is available at www.celgeneriskmanagement.com or by calling the manufacturer’s toll-free number 1-888-423-5436.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks.

Please see additional Important Safety Information throughout presentation.

REVLIMID was studied in transfusion-dependent patients with LOW TO INTERMEDIATE-1 del 5q MDS ± additional cytogenetic abnormalities1,2

MDS pivotal trial

Multicenter, single-arm,
open-label study enrolled
148 patients
who had RBC
transfusion-dependent
low- or intermediate-1–risk
MDS with del 5q (q31-33)
with or without additional
cytogenetic abnormalitiesa

Patients received
REVLIMID 10 mg
once dailyb,c (n=102)

Revlimid Pill 10mg

or 10 mg once daily for
21 days every 28 daysb,c
(n=46)

Primary End Point:

RBC transfusion
independenced

Secondary End Points:

Duration of transfusion
independenced

Cytogenetic responsee

Click to view additional inclusion criteriaf

  • Low- or intermediate-1–risk MDS
  • Patients 18 years and older with an ECOG status of 0, 1, or 2
  • Transfusion-dependent anemia (≥2 units RBC/8 weeks prior to study treatment)
  • Deletion 5q (q31-33) cytogenetic abnormality in isolation or with additional cytogenetic abnormalities
  • ANC ≥500/mm3
  • Platelets ≥50,000/mm3
  • Serum creatinine ≤2.5 mg/dL
  • Serum SGOT/AST or SGPT/ALT ≤3 x ULN
  • Serum direct bilirubin ≤2.0 mg/dL

aThe study was not designed or powered to prospectively compare the efficacy of the 2 dosing regimens.

bSequential dose reductions to 5 mg/day and 5 mg every other day, as well as dose delays, were allowed for toxicity.

cG-CSF was permitted for patients who developed neutropenia or fever associated with neutropenia.

dRBC transfusion independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 56 days (8 weeks) during the treatment period.

eCytogenetic response was defined as the complete absence of or at least 50% reduction of cells containing any abnormal clone.

fAdditional criteria may apply.

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CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus

Severe Hypersensitivity Reactions: REVLIMID is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide

Please see additional Important Safety Information throughout presentation.

Baseline Patient Characteristics1

Age

In the MDS pivotal trial
(N=148)

Median age was

71 Years

(range: 37-95)

33%

of patients were
>75 years of age

Included patients
up to

95 Years

of age

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WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS

  • Blood Donation: Patients must not donate blood during treatment with REVLIMID and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to REVLIMID

Please see additional Important Safety Information throughout presentation.

Baseline Patient Characteristics1

Cytogenetics

In the MDS pivotal trial
(N=148)

100%

of patients had del 5q (q31-33) cytogenetic abnormality

25%

of patients had additional cytogenetic abnormalities

IPSS

In the MDS pivotal trial
(N=148)

81%

of patients were low- or intermediate-1–risk

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WARNINGS AND PRECAUTIONS (CONT'D)

REVLIMID REMS® Program: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements

Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. MDS: Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or dose reduction. Please see the Black Box WARNINGS for further information

Please see additional Important Safety Information throughout presentation.

Baseline Patient Characteristics1

Transfusion Dependency

In the MDS pivotal trial
(N=148)

100%

of patients were transfusion dependent

Defined as

≥2 units RBC/
8 weeks

prior to treatment

Click to view additional baseline characteristics

Characteristic N=148
Median age (range), years 71 (37-95)
Male:female, n (%) 51 (34.5):97 (65.5)
White race, n (%) 143 (96.6)
Median duration of MDS (range), years 2.5 (0.1-20.7)
del 5q (q31-33) cytogenetic abnormality, n (%) 148 (100)
Other cytogenetic abnormalities, n (%) 37 (25.2)
IPSS score, n (%)
Low (0) 55 (37.2)
Intermediate-1 (0.5-1.0) 65 (43.9)
Intermediate-2 (1.5-2.0) 6 (4.1)
High (≥2.5) 2 (1.4)
Missing 20 (13.5)
FAB classification from central review, n (%)
RA 77 (52)
RARS 16 (10.8)
RAEB 30 (20.3)
CMML 3 (2)

CMML=chronic myelomonocytic leukemia; FAB=French-American-British; RA=refractory anemia; RAEB=RA with excess blasts; RARS=RA with ringed sideroblasts.

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WARNINGS AND PRECAUTIONS (CONT'D)

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended and the regimen should be based on patient’s underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision

Increased Mortality in Patients with CLL: In a clinical trial in the first-line treatment of patients with CLL, single agent REVLIMID therapy increased the risk of death as compared to single agent chlorambucil. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Please see additional Important Safety Information throughout presentation.

Select an answer to see how others responded

How many of your patients with lower-risk del 5q mds are able to achieve transfusion independence?

How many of your patients with lower-risk del 5q MDS are able to achieve transfusion independence?

how others responded

0%

0% to <10%

50%

10% to <25%

100%

25% to <50%

0%

50% to <75%

0%

75% to 100%

Scroll down to discover REVLIMID's efficacy

Select Important Safety Information

WARNINGS AND PRECAUTIONS (CONT'D)

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID, an increase of hematologic plus solid tumor SPM, notably AML and MDS, have been observed. Monitor patients for the development of SPM. Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment

Increased Mortality with Pembrolizumab: In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered

Please see additional Important Safety Information throughout presentation.

Cut Transfusion Dependence Out of MDS1


Proven efficacy of REVLIMID in del 5q MDS ± additional cytogenetic abnormalities

67%

of patients (99/148) achieved transfusion independence

RBC transfusion independence rates were unaffected by age or gender

RBC transfusion independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 56 days (8 weeks) during the treatment period.

The frequency of RBC transfusion independence was assessed using criteria modified from the International Working Group (IWG) response criteria for MDS.

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WARNINGS AND PRECAUTIONS (CONT'D)

Severe Cutaneous Reactions Including Hypersensitivity Reactions: Angioedema and severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash, or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS, TEN, or DRESS is suspected and should not be resumed following discontinuation for these reactions

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Please see additional Important Safety Information throughout presentation.

MEDIAN HEMOGLOBIN LEVELS2


Median increase in hemoglobina was 5.4 g/dL (1.1-11.4) in patients achieving transfusion independence (n=99/148)

  • 4 patients developed erythrocytosis, with hemoglobin levels >17 g/dL

aAt least 1 g/dL rise in hemoglobin was part of the criteria for achieving transfusion independence, the primary end point.

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WARNINGS AND PRECAUTIONS (CONT'D)

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to ≤Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician’s discretion

Please see additional Important Safety Information throughout presentation.

Durable Response1,2


in del 5q MDS ± additional cytogenetic abnormalities

At interim analysisa

Weeks 44

median duration of RBC transfusion independenceb

(range: 0 to >67), n=99/148

Some patients maintained transfusion independence beyond 67 weeks at interim analysis

Treatment is continued or modified based upon clinical and laboratory findings.

80% of patients (118/148) had to have a dose interruption/reduction and 34% of patients (50/148) had to have a second dose interruption/reduction

aInterim analysis of 99 responders (data cutoff: July 15, 2005).

bFrequency of RBC transfusion independence was assessed using criteria modified from the International Working Group (IWG) response criteria.

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WARNINGS AND PRECAUTIONS (CONT'D)

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treatment and during therapy

Early Mortality in Patients with MCL: In another MCL study, there was an increase in early deaths (within 20 weeks), 12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk factors for early deaths include high tumor burden, MIPI score at diagnosis, and high WBC at baseline (≥10 x 109/L)

Please see additional Important Safety Information throughout presentation.

LONG-TERM DURATION OF RESPONSE3


at a median follow-up of 3.2 years (range: 0.3‑6.8)a

Weeks 44

median duration of RBC transfusion independenceb

(range: 1.5-2.9), n=97/148

Some patients maintained transfusion independence at long-term follow-up

Treatment is continued or modified based upon clinical and laboratory findings.

80% of patients (118/148) had to have a dose interruption/reduction and 34% of patients (50/148) had to have a second dose interruption/reduction

aLong-term follow-up of 97 responders (data cutoff: October 8, 2010).

bFrequency of RBC transfusion independence was assessed using criteria modified from the International Working Group (IWG) response criteria.

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ADVERSE REACTIONS

Myelodysplastic Syndromes

  • Grade 3 and 4 adverse events reported in ≥ 5% of patients with del 5q MDS were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain (5%)
  • Adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection (15%)

Please see additional Important Safety Information throughout presentation.

Select an answer to see how others responded

to achieve transfusion independence with revlimid, how long would you wait?

To achieve transfusion independence with REVLIMID, how long would you wait?

how others responded

0%

<1 month

50%

1 to 2 months

100%

2 to 3 months

0%

3 to 4 months

0%

>4 months

Scroll down for additional efficacy information

Select Important Safety Information

DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels is recommended due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin

Please see additional Important Safety Information throughout presentation.

Give your patients the time to achieve transfusion benefit1


The majority of patients achieved an RBC transfusion benefit by 3 months with REVLIMID

90%

of patients (90/99) achieved transfusion independence by

Months 3

of treatment

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USE IN SPECIFIC POPULATIONS

  • PREGNANCY: See Boxed WARNINGS: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a REVLIMID pregnancy exposure registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy as well as female partners of male patients who are exposed to REVLIMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1‑888‑423‑5436
  • LACTATION: There is no information regarding the presence of lenalidomide in human milk, the effects of REVLIMID on the breastfed infant, or the effects of REVLIMID on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from REVLIMID, advise female patients not to breastfeed during treatment with REVLIMID

Please see additional Important Safety Information throughout presentation.

CYTOGENETIC RESPONSE3


in del 5q MDS ± additional cytogenetic abnomalities evaluated in a non-interventional extension study

Response rate (n/N) Median time to response
Cytogenetic responsea,b (CR+PR) 72%
(63/88)
5.0 months
(95% Cl, 4.8‑5.3)
Complete cytogenetic remissiona (CR) 46%
(40/88)
4.9 months
(95% Cl, 4.7‑5.1)
Partial cytogenetic responsea (PR) 26%
(23/88)
5.4 months
(95% Cl, 5.0‑5.8)
  • Cytogenetic response was evaluated in 88 patients with ≥20 bone marrow cells in metaphase at baseline and during active treatment by an independent cytogenetic reviewer
  • Median time to cytogenetic response was based on 63 patients who achieved a cytogenetic response at a median follow-up of 3.2 years (range: 0.03-6.8)
    • 25 of the complete responders (40%, n=25/63) maintained the complete response during follow-up
  • Analysis of cytogenetic response was independent from the analysis of transfusion independence

aComplete cytogenetic remission was defined as the absence of cells in metaphase containing any abnormal clone. Partial cytogenetic response was defined as a reduction of at least 50% of cells in metaphase containing any abnormal clone.

bData cutoff: October 8, 2010.

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USE IN SPECIFIC POPULATIONS (CONT'D)

  • PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients
  • RENAL IMPAIRMENT: Adjust the starting dose of REVLIMID based on creatinine clearance value and in patients on dialysis

Please see additional Important Safety Information throughout presentation.

Choose REVLIMID first


For patients with low- or intermediate-1–risk del 5q MDS ± additional cytogenetic abnormalities1

REVLIMID® (lenalidomide) is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1–risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

REVLIMID is only available through a restricted distribution program, REVLIMID REMS®.

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colleagues approach
treatment with REVLIMID?

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