Pomalyst

— THERAPEUTIC DISORDERS TREATED —
  • Kaposi's sarcoma
  • Leukemias, lymphomas, and other hematologic cancers
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Pomalyst Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Pomalidomide 1mg, 2mg, 3mg, 4mg; caps.

    Pharmacological Class

    Immunomodulator.

    How Supplied

    Caps—21, 100

    How Supplied

    Pomalyst is supplied in:

    Dark blue opaque cap and yellow opaque body, imprinted “POML” on the cap in white ink and “1 mg” on the body in black ink

    • 1 mg bottles of 21
    • 1 mg bottles of 100

    Dark blue opaque cap and orange opaque body, imprinted “POML” on the cap and “2 mg” on the body in white ink

    • 2 mg bottles of 21
    • 2 mg bottles of 100

    Dark blue opaque cap and green opaque body, imprinted “POML” on the cap and “3 mg” on the body in white ink

    • 3 mg bottles of 21
    • 3 mg bottles of 100

    Dark blue opaque cap and blue opaque body, imprinted “POML” on the cap and “4 mg” on the body in white ink

    • 4 mg bottles of 21
    • 4 mg bottles of 100 

    Storage

    Store at 20° C to 25° C (68° F to 77° F); excursions permitted to 15° C to 30° C (59° F to 86° F).

    Manufacturer

    Celgene Corp

    Generic Availability

    YES

    Pomalyst Indications

    Indications

    AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) in adults. Kaposi sarcoma in HIV-negative adults.

    Indications

    This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

    Pomalyst Dosage and Administration

    Adult

    Confirm negative pregnancy status before initiation. Swallow whole; may be taken with water (with or without food). 5mg once daily on Days 1–21 of each 28-day cycle until disease progression or unacceptable toxicity; continue HAART in AIDS patients. Concomitant strong CYP1A2 inhibitors (if unavoidable): reduce Pomalyst dose to 2mg. Severe renal impairment requiring dialysis: 4mg daily; give dose after dialysis session on hemodialysis days. Hepatic impairment: 3mg daily. Dose modifications for adverse reactions, other Grade 3/4 toxicities: see full labeling.

    Children

    Not established.

    Renal Impairment

    In patients with severe renal impairment requiring dialysis, the AUC of pomalidomide increased by 38% and the rate of SAE increased by 64% relative to patients with normal renal function; therefore, starting dose adjustment is recommended. For patients with severe renal impairment requiring dialysis, administer pomalidomide after the completion of hemodialysis on dialysis days because exposure of pomalidomide could be significantly decreased during dialysis.

    Hepatic Impairment

    Pomalidomide is metabolized primarily by the liver. Following single dose administration, the AUC of pomalidomide increased 51%, 58%, and 72% in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment, respectively compared to subjects with normal liver function. Dose adjustment is recommended in patients with hepatic impairment.

    Pomalyst Contraindications

    Contraindications

    Pregnancy.

    Pomalyst Boxed Warnings

    Boxed Warning

    Embryo-fetal toxicity. Venous and arterial thromboembolism.

    Boxed Warning

    Embryo-fetal toxicity

    • Pomalidomide is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting pomalidomide treatment.
    • Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping pomalidomide treatment.

    Venous and arterial thromboembolism

    • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with pomalidomide. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.

    Pomalyst Warnings/Precautions

    Warnings/Precautions

    Embryo-fetal toxicity: females of reproductive potential must avoid pregnancy, commit either to abstain from heterosexual sex or to use two methods of reliable contraception, at least 4 weeks prior to initiating, during therapy, dose interruptions and for at least 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24hrs prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 4 weeks after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation. Venous and arterial thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); withhold, reduce dose, or permanently discontinue based on severity of reaction. Obtain CBCs weekly for first 8 weeks (for MM) or every 2 weeks for first 12 weeks (for KS), and monthly thereafter. Hepatic or severe renal impairment on hemodialysis: adjust doses (see Adults). Monitor LFTs monthly; discontinue and evaluate if elevated liver enzymes occur; consider using lower dose when restarting. Risk of second primary malignancies. High tumor burden (monitor). Permanently discontinue if angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or other severe cutaneous reactions occur (eg, SJS, TEN, DRESS). Nursing mothers: not recommended.

    Warnings/Precautions

    Embryo-fetal toxicity

    See Boxed Warnings and Contraindications.

    Females of Reproductive Potential 

    • Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning pomalidomide therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of pomalidomide therapy. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing pomalidomide therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles, or every 2 weeks in females with irregular menstrual cycles.

    Males 

    • Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 4 weeks after discontinuing pomalidomide, even if they have undergone a successful vasectomy. Male patients taking pomalidomide must not donate sperm.

    Blood Donation 

    • Patients must not donate blood during treatment with pomalidomide 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 pomalidomide.

    Venous and arterial thromboembolism

    See Boxed Warnings.

    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 (eg, hyperlipidemia, hypertension, smoking).

    Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone

    In two randomized clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with MM 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.

    Hematologic Toxicity  

    Multiple Myeloma

    • Monitor patients for hematologic toxicities, especially neutropenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.

    Kaposi Sarcoma

    • Monitor patients for hematologic toxicities, especially decreased neutrophils. Monitor complete blood counts every 2 weeks for the first 12 weeks and monthly thereafter. Withhold, reduce the dose, or permanently discontinue pomalidomide based on the severity of the reaction.

    Hepatotoxicity  

    Hepatic failure, including fatal cases, has occurred in patients treated with pomalidomide. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with pomalidomide. Monitor liver function tests monthly. Stop pomalidomide upon elevation of liver enzymes and evaluate. After returning to baseline values, treatment at a lower dose may be considered. 

    Severe Cutaneous Reactions  

    Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. These reactions can be fatal. Consider pomalidomide interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue pomalidomide for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS.

    Risk of Second Primary Malignancies 

    Cases of acute myelogenous leukemia have been reported in patients receiving pomalidomide as an investigational therapy outside of MM.

    Tumor Lysis Syndrome 

    Tumor lysis syndrome (TLS) may occur in patients treated with pomalidomide. Patients at risk for TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. 

    Hypersensitivity 

    Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to pomalidomide have been reported. Permanently discontinue pomalidomide for angioedema or anaphylaxis.

    Pregnancy Considerations

    Based on the mechanism of action and findings from animal studies, pomalidomide can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy.

    Pomalidomide is a thalidomide analogue. Thalidomide is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects.

    Nursing Mother Considerations

    There is no information regarding the presence of pomalidomide in human milk, the effects of pomalidomide on the breastfed child, or the effects of pomalidomide on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child from pomalidomide, advise women not to breastfeed during treatment with pomalidomide.

    Following a single oral administration of pomalidomide to lactating rats approximately 14 days postpartum, pomalidomide was transferred into milk, with milk to plasma ratios of 0.63 to 1.46.

    Pediatric Considerations

    The safety and effectiveness of pomalidomide have not been established in pediatric patients. The safety and effectiveness were assessed but not established in two open-label studies: a dose escalation study in 25 pediatric patients aged 5 to <17 with recurrent, progressive or refractory CNS tumors [NCT02415153] and a parallel group study conducted in 47 pediatric patients aged 4 to <17 years with recurrent or progressive high-grade glioma, medulloblastoma, ependymoma, or diffuse intrinsic pontine glioma (DIPG) [NCT03257631]. No new safety signals were observed in pediatric patients across these studies. 

    At the same dose by body surface area, pomalidomide exposure in 55 pediatric patients aged 4 to < 17 years old was within the range observed in adult patients with MM but higher than the exposure observed in adult patients with KS.

    Geriatric Considerations

    Multiple Myeloma

    No overall differences in effectiveness were observed between these patients and younger patients. In these studies, patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia.

    Kaposi Sarcoma

    The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. 

    Renal Impairment Considerations

    In patients with severe renal impairment requiring dialysis, the AUC of pomalidomide increased by 38% and the rate of SAE increased by 64% relative to patients with normal renal function; therefore, starting dose adjustment is recommended. For patients with severe renal impairment requiring dialysis, administer pomalidomide after the completion of hemodialysis on dialysis days because exposure of pomalidomide could be significantly decreased during dialysis.

    Hepatic Impairment Considerations

    Pomalidomide is metabolized primarily by the liver. Following single dose administration, the AUC of pomalidomide increased 51%, 58%, and 72% in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment, respectively compared to subjects with normal liver function. Dose adjustment is recommended in patients with hepatic impairment.

    REMS

    YES

    Pomalyst Pharmacokinetics

    Absorption

    Following administration of single oral doses of pomalidomide, the maximum plasma concentration (Cmax) for pomalidomide occurs at 2 to 3 hours postdose in patients with MM or KS.

    Distribution

    Human plasma protein binding of pomalidomide ranges from 12% to 44% and is not concentration dependent.

    Metabolism

    Pomalidomide is primarily metabolized in the liver by CYP1A2 and CYP3A4. Minor contributions from CYP2C19 and CYP2D6 were also observed in vitro.

    Elimination

    Pomalidomide is eliminated with a median plasma half-life of 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS.

    Following a single oral administration of [14C]-pomalidomide to healthy subjects, ~73% and 15% of the radioactive dose was eliminated in urine and feces, respectively, with ~2% and 8% of the radiolabeled dose eliminated unchanged as pomalidomide in urine and feces.

    Pomalyst Interactions

    Interactions

    Increased mortality when PD-1 or PD-L1 blocking antibody (eg, pembrolizumab) is added to thalidomide analogue plus dexamethasone regimen in multiple myeloma: not recommended. Potentiated by strong CYP1A2 inhibitors (eg, ciprofloxacin, fluvoxamine); avoid (see Adults). Smoking may reduce efficacy.

    Interactions

    Drugs That Affect Pomalidomide Plasma Concentrations

    • CYP1A2 inhibitors:
      • In healthy subjects, co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased Cmax and AUC of pomalidomide by 24% and 125% respectively. Increased pomalidomide exposure may increase the risk of exposure related toxicities.
      • Avoid co-administration of strong CYP1A2 inhibitors (eg, ciprofloxacin and fluvoxamine). If co-administration is unavoidable, reduce the pomalidomide dose.

    Increased mortality when PD-1 or PD-L1 blocking antibody (eg, pembrolizumab) is added to thalidomide analogue plus dexamethasone regimen in multiple myeloma: not recommended. 

    Cigarette smoking reduces pomalidomide AUC due to CYP1A2 induction. Advise patients that smoking may reduce the efficacy of pomalidomide.

    Pomalyst Adverse Reactions

    Adverse Reactions

    Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infections, back pain, pyrexia, rash, elevated creatinine, glucose, or ALT, decreased hemoglobin, platelets, phosphate, albumin, or calcium; thrombocytopenia, hepatotoxicity, dizziness, confusion, neuropathy, pneumonia, tumor lysis syndrome, severe cutaneous or hypersensitivity reactions.

    Adverse Reactions

    Multiple myeloma

    Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.

    Kaposi sarcoma

    Most common adverse reactions including laboratory abnormalities (≥30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea.

     

    Pomalyst Clinical Trials

    Clinical Trials

    Multiple Myeloma  
    Trial 1 was a phase 2, multicenter, randomized open-label study in patients with relapsed multiple myeloma (MM) who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib. Patients were considered relapsed if they had achieved at least stable disease for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease. Patients were considered refractory if they experienced disease progression on or within 60 days of their last therapy. A total of 221 patients were randomized to receive pomalidomide alone or pomalidomide with Low-dose Dex. In Trial 1, the safety and efficacy of pomalidomide 4 mg, once daily for 21 of 28 days, until disease progression, were evaluated alone and in combination with Low-dose Dex (40 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged 75 years or younger, or 20 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged greater than 75 years). Patients in the pomalidomide alone arm were allowed to add Low-dose Dex upon disease progression.

    The trial was designed to measure the number of patients whose cancer completely or partially disappeared after treatment (objective response rate, or ORR). The analysis results showed 7.4% (95% CI, 3.3-14.1) of patients treated with Pomalyst alone achieved ORR. In patients treated with Pomalyst plus low-dose dexamethasone, 29.2% (95% CI, 21-38.5) achieved ORR with a 7.4-month (95% CI, 5.1-9.2) median duration of response.

    Trial 2 was a Phase 3 multi-center, randomized, open-label study, where Pomalyst + Low-dose Dex therapy was compared to High-dose Dex in adult patients with relapsed and refractory MM, who had received at least two prior treatment regimens, including lenalidomide and bortezomib, and demonstrated disease progression on or within 60 days of the last therapy. A total of 455 patients were enrolled in the trial: 302 in the Pomalyst + Low-dose Dex arm and 153 in the High-dose Dex arm. Patients in the Pomalyst + Low-dose Dex arm were administered 4 mg Pomalyst orally on Days 1 to 21 of each 28-day cycle. Dexamethasone (40 mg) was administered once per day on Days 1, 8, 15 and 22 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. For the High-dose Dex arm, dexamethasone (40 mg) was administered once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. Treatment continued until patients had disease progression. 

    The primary endpoints assessed were progression free survival (PFS), overall response rate (ORR), and overall survival (OS), which were based on the evaluation by the Independent Review Adjudication Committee (IRAC). 

    Results showed that PFS was significantly longer with Pomalyst + Low-dose Dex versus High-dose Dex: HR 0.45 (95% CI, 0.35-0.59; P <0.001). OS was also significantly longer with Pomalyst + Low-dose Dex compared to High-dose Dex: HR 0.70 (95% CI, 0.54-0.92; P =0.009). In addition, the ORR was also higher with Pomalyst + Low-dose Dex compared to High-dose Dex (23.5% vs 3.9%), respectively.

    Kaposi Sarcoma 
    The clinical trial 12-C-0047 (NCT01495598), was an open label, single center, single arm clinical study that evaluated the safety and efficacy of Pomalyst in patients with Kaposi sarcoma (KS). A total of 28 patients (18 HIV-positive, 10 HIV-negative) received Pomalyst 5 mg orally once daily on Days 1 through 21 of each 28-day cycle until disease progression or unacceptable toxicity. All HIV-positive patients continued highly active antiretroviral therapy (HAART). Patients received thromboprophylaxis with aspirin 81 mg once daily throughout therapy. Seventy five percent of patients had advanced disease (T1) at the time of enrollment, 11% had ≥ 50 lesions, and 75% had received prior chemotherapy. The major efficacy outcome measure was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR), and partial response (PR). Response was assessed by the investigator according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for KS. The median time to first response was 1.8 months (0.9-7.6).

    Results showed an ORR of 71% (95% CI, 51-87) among all patients, with a median duration of response of 12.1 months (95% CI, 7.6-16.8). Among HIV-positive patients, the ORR was 67% (95% CI, 41-87), with a median duration of response of 12.5 months (95% CI, 6.5-24.9). An ORR of 80% (95% CI, 44-98) was observed among HIV-negative patients, with a median duration of response of 10.5 months (95% CI, 3.9-24.2). 

    Pomalyst Note

    Notes

    Available only through Pomalyst REMS program. More information about the Pomalyst REMS program is available at www.celgeneriskmanagement.com or call (888) 423-5436.

    Pomalyst Patient Counseling

    Patient Counseling

    Embryo-Fetal Toxicity 
    Advise patients that pomalidomide is contraindicated in pregnancy. Pomalidomide is a thalidomide analogue and may cause serious birth defects or death to a developing baby.

    • Advise females of reproductive potential that they must avoid pregnancy while taking Pomalidomide and for at least 4 weeks after completing therapy.  
    • Initiate pomalidomide treatment in females of reproductive potential only following a negative pregnancy test.
    • Advise females of reproductive potential of the importance of monthly pregnancy tests and the need to use 2 different forms of contraception, including at least 1 highly effective form, simultaneously during pomalidomide therapy, during dose interruptions, and for 4 weeks after she has completely finished taking pomalidomide. Highly effective forms of contraception other than tubal ligation include IUD and hormonal (birth control pills, injections, patch, or implants) and a partner’s vasectomy. Additional effective contraceptive methods include latex or synthetic condom, diaphragm, and cervical cap.
    • Instruct patient to immediately stop taking pomalidomide and contact her healthcare provider if she becomes pregnant while taking this drug, if she misses her menstrual period or experiences unusual menstrual bleeding, if she stops taking birth control, or if she thinks FOR ANY REASON that she may be pregnant.
    • Advise males to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 4 weeks after discontinuing pomalidomide, even if they have undergone a successful vasectomy.
    • Advise male patients taking pomalidomide that they must not donate sperm.
    • All patients must be instructed to not donate blood while taking pomalidomide and for 4 weeks following discontinuation of pomalidomide.

    Venous and Arterial Thromboembolism 

    Inform patients of the risk of developing DVT, PE, MI, and stroke and to report immediately any signs and symptoms suggestive of these events for evaluation.

    Hematologic Toxicities 

    Inform patients on the risks of developing neutropenia, thrombocytopenia, and anemia and the need to report signs and symptoms associated with these events to their healthcare provider for further evaluation.

    Hepatotoxicity 

    Inform patients on the risks of developing hepatotoxicity, including hepatic failure and death, and to report signs and symptoms associated with these events to their healthcare provider for evaluation.

    Severe Cutaneous Reactions 

    Inform patients of the potential risk for severe skin reactions such as SJS, TEN and DRESS and to report any signs and symptoms associated with these reactions to their healthcare provider for evaluation.

    Dizziness and Confusional State 

    Inform patients of the potential risk of dizziness and confusional state with the drug, to avoid situations where dizziness or confusional state may be a problem, and not to take other medications that may cause dizziness or confusional state without adequate medical advice.

    Neuropathy 

    Inform patients of the risk of neuropathy and to report the signs and symptoms associated with these events to their healthcare provider for further evaluation.

    Second Primary Malignancies 

    Inform the patient that the potential risk of developing acute myelogenous leukemia during treatment with pomalidomide is unknown.

    Tumor Lysis Syndrome 

    Inform patients of the potential risk of tumor lysis syndrome and to report any signs and symptoms associated with this event to their healthcare provider for evaluation.

    Hypersensitivity 

    Inform patients of the potential for severe hypersensitivity reactions such as angioedema and anaphylaxis to pomalidomide. Instruct patients to contact their healthcare provider right away for any signs and symptoms of these reactions. Advise patients to seek emergency medical attention for signs or symptoms of severe hypersensitivity reactions.

    Smoking Tobacco 

    Advise patients that smoking tobacco may reduce the efficacy of pomalidomide.

    Cost Savings Program

    The Pomalyst savings program is available here.

    Pomalyst Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Pomalidomide 1mg, 2mg, 3mg, 4mg; caps.

    Pharmacological Class

    Immunomodulator.

    How Supplied

    Caps—21, 100

    How Supplied

    Pomalyst is supplied in:

    Dark blue opaque cap and yellow opaque body, imprinted “POML” on the cap in white ink and “1 mg” on the body in black ink

    • 1 mg bottles of 21
    • 1 mg bottles of 100

    Dark blue opaque cap and orange opaque body, imprinted “POML” on the cap and “2 mg” on the body in white ink

    • 2 mg bottles of 21
    • 2 mg bottles of 100

    Dark blue opaque cap and green opaque body, imprinted “POML” on the cap and “3 mg” on the body in white ink

    • 3 mg bottles of 21
    • 3 mg bottles of 100

    Dark blue opaque cap and blue opaque body, imprinted “POML” on the cap and “4 mg” on the body in white ink

    • 4 mg bottles of 21
    • 4 mg bottles of 100 

    Storage

    Store at 20° C to 25° C (68° F to 77° F); excursions permitted to 15° C to 30° C (59° F to 86° F).

    Manufacturer

    Celgene Corp

    Generic Availability

    YES

    Pomalyst Indications

    Indications

    In combination with dexamethasone for multiple myeloma (MM), in patients who have received at least two prior therapies (including lenalidomide and a proteasome inhibitor), and have shown disease progression on or within 60 days of completion of the last therapy.

    Pomalyst Dosage and Administration

    Prior to Treatment Evaluations

    Pregnancy Testing Prior to Administration 

    Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating pomalidomide.

    Adult

    Confirm negative pregnancy status before initiation. Swallow whole; may be taken with water (with or without food). 4mg once daily on Days 1–21 of each 28-day cycle until disease progression; give with dexamethasone. Concomitant strong CYP1A2 inhibitors (if unavoidable): reduce Pomalyst dose to 2mg. Severe renal impairment requiring dialysis: 3mg daily; give dose after dialysis session on hemodialysis days. Hepatic impairment (mild or moderate): 3mg daily; (severe): 2mg daily. Dose modifications for adverse reactions, other Grade 3/4 toxicities: see full labeling.

    Children

    Not established.

    Renal Impairment

    In patients with severe renal impairment requiring dialysis, the AUC of pomalidomide increased by 38% and the rate of SAE increased by 64% relative to patients with normal renal function; therefore, starting dose adjustment is recommended. For patients with severe renal impairment requiring dialysis, administer pomalidomide after the completion of hemodialysis on dialysis days because exposure of pomalidomide could be significantly decreased during dialysis.

    Hepatic Impairment

    Pomalidomide is metabolized primarily by the liver. Following single dose administration, the AUC of pomalidomide increased 51%, 58%, and 72% in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment, respectively compared to subjects with normal liver function. Dose adjustment is recommended in patients with hepatic impairment.

    Pomalyst Contraindications

    Contraindications

    Pregnancy.

    Pomalyst Boxed Warnings

    Boxed Warning

    Embryo-fetal toxicity. Venous and arterial thromboembolism.

    Boxed Warning

    Embryo-fetal toxicity

    • Pomalidomide is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting pomalidomide treatment.
    • Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping pomalidomide treatment.

    Venous and arterial thromboembolism

    • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with pomalidomide. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.

    Pomalyst Warnings/Precautions

    Warnings/Precautions

    Embryo-fetal toxicity: females of reproductive potential must avoid pregnancy, commit either to abstain from heterosexual sex or to use two methods of reliable contraception, at least 4 weeks prior to initiating, during therapy, dose interruptions and for at least 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24hrs prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 4 weeks after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation. Venous and arterial thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); withhold, reduce dose, or permanently discontinue based on severity of reaction. Obtain CBCs weekly for first 8 weeks (for MM) or every 2 weeks for first 12 weeks (for KS), and monthly thereafter. Hepatic or severe renal impairment on hemodialysis: adjust doses (see Adults). Monitor LFTs monthly; discontinue and evaluate if elevated liver enzymes occur; consider using lower dose when restarting. Risk of second primary malignancies. High tumor burden (monitor). Permanently discontinue if angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or other severe cutaneous reactions occur (eg, SJS, TEN, DRESS). Nursing mothers: not recommended.

    Warnings/Precautions

    Embryo-fetal toxicity

    See Boxed Warnings and Contraindications.

    Females of Reproductive Potential 

    • Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning pomalidomide therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of pomalidomide therapy. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing pomalidomide therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles, or every 2 weeks in females with irregular menstrual cycles.

    Males 

    • Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 4 weeks after discontinuing pomalidomide, even if they have undergone a successful vasectomy. Male patients taking pomalidomide must not donate sperm.

    Blood Donation 

    • Patients must not donate blood during treatment with pomalidomide 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 pomalidomide.

    Venous and arterial thromboembolism

    See Boxed Warnings.

    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 (eg, hyperlipidemia, hypertension, smoking).

    Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone

    In two randomized clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with MM 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.

    Hematologic Toxicity  

    Multiple Myeloma

    • Monitor patients for hematologic toxicities, especially neutropenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.

    Kaposi Sarcoma

    • Monitor patients for hematologic toxicities, especially decreased neutrophils. Monitor complete blood counts every 2 weeks for the first 12 weeks and monthly thereafter. Withhold, reduce the dose, or permanently discontinue pomalidomide based on the severity of the reaction.

    Hepatotoxicity  

    Hepatic failure, including fatal cases, has occurred in patients treated with pomalidomide. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with pomalidomide. Monitor liver function tests monthly. Stop pomalidomide upon elevation of liver enzymes and evaluate. After returning to baseline values, treatment at a lower dose may be considered. 

    Severe Cutaneous Reactions  

    Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. These reactions can be fatal. Consider pomalidomide interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue pomalidomide for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS.

    Risk of Second Primary Malignancies 

    Cases of acute myelogenous leukemia have been reported in patients receiving pomalidomide as an investigational therapy outside of MM.

    Tumor Lysis Syndrome 

    Tumor lysis syndrome (TLS) may occur in patients treated with pomalidomide. Patients at risk for TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. 

    Hypersensitivity 

    Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to pomalidomide have been reported. Permanently discontinue pomalidomide for angioedema or anaphylaxis.

    Pregnancy Considerations

    Based on the mechanism of action and findings from animal studies, pomalidomide can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy.

    Pomalidomide is a thalidomide analogue. Thalidomide is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects.

    Nursing Mother Considerations

    There is no information regarding the presence of pomalidomide in human milk, the effects of pomalidomide on the breastfed child, or the effects of pomalidomide on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child from pomalidomide, advise women not to breastfeed during treatment with pomalidomide.

    Following a single oral administration of pomalidomide to lactating rats approximately 14 days postpartum, pomalidomide was transferred into milk, with milk to plasma ratios of 0.63 to 1.46.

    Pediatric Considerations

    The safety and effectiveness of pomalidomide have not been established in pediatric patients. The safety and effectiveness were assessed but not established in two open-label studies: a dose escalation study in 25 pediatric patients aged 5 to <17 with recurrent, progressive or refractory CNS tumors [NCT02415153] and a parallel group study conducted in 47 pediatric patients aged 4 to <17 years with recurrent or progressive high-grade glioma, medulloblastoma, ependymoma, or diffuse intrinsic pontine glioma (DIPG) [NCT03257631]. No new safety signals were observed in pediatric patients across these studies. 

    At the same dose by body surface area, pomalidomide exposure in 55 pediatric patients aged 4 to < 17 years old was within the range observed in adult patients with MM but higher than the exposure observed in adult patients with KS.

    Geriatric Considerations

    Multiple Myeloma

    No overall differences in effectiveness were observed between these patients and younger patients. In these studies, patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia.

    Kaposi Sarcoma

    The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. 

    Renal Impairment Considerations

    In patients with severe renal impairment requiring dialysis, the AUC of pomalidomide increased by 38% and the rate of SAE increased by 64% relative to patients with normal renal function; therefore, starting dose adjustment is recommended. For patients with severe renal impairment requiring dialysis, administer pomalidomide after the completion of hemodialysis on dialysis days because exposure of pomalidomide could be significantly decreased during dialysis.

    Hepatic Impairment Considerations

    Pomalidomide is metabolized primarily by the liver. Following single dose administration, the AUC of pomalidomide increased 51%, 58%, and 72% in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment, respectively compared to subjects with normal liver function. Dose adjustment is recommended in patients with hepatic impairment.

    REMS

    YES

    Pomalyst Pharmacokinetics

    Absorption

    Following administration of single oral doses of pomalidomide, the maximum plasma concentration (Cmax) for pomalidomide occurs at 2 to 3 hours postdose in patients with MM or KS.

    Distribution

    Human plasma protein binding of pomalidomide ranges from 12% to 44% and is not concentration dependent.

    Metabolism

    Pomalidomide is primarily metabolized in the liver by CYP1A2 and CYP3A4. Minor contributions from CYP2C19 and CYP2D6 were also observed in vitro.

    Elimination

    Pomalidomide is eliminated with a median plasma half-life of 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS.

    Following a single oral administration of [14C]-pomalidomide to healthy subjects, ~73% and 15% of the radioactive dose was eliminated in urine and feces, respectively, with ~2% and 8% of the radiolabeled dose eliminated unchanged as pomalidomide in urine and feces.

    Pomalyst Interactions

    Interactions

    Increased mortality when PD-1 or PD-L1 blocking antibody (eg, pembrolizumab) is added to thalidomide analogue plus dexamethasone regimen in multiple myeloma: not recommended. Potentiated by strong CYP1A2 inhibitors (eg, ciprofloxacin, fluvoxamine); avoid (see Adults). Smoking may reduce efficacy.

    Interactions

    Drugs That Affect Pomalidomide Plasma Concentrations

    • CYP1A2 inhibitors:
      • In healthy subjects, co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased Cmax and AUC of pomalidomide by 24% and 125% respectively. Increased pomalidomide exposure may increase the risk of exposure related toxicities.
      • Avoid co-administration of strong CYP1A2 inhibitors (eg, ciprofloxacin and fluvoxamine). If co-administration is unavoidable, reduce the pomalidomide dose.

    Increased mortality when PD-1 or PD-L1 blocking antibody (eg, pembrolizumab) is added to thalidomide analogue plus dexamethasone regimen in multiple myeloma: not recommended. 

    Cigarette smoking reduces pomalidomide AUC due to CYP1A2 induction. Advise patients that smoking may reduce the efficacy of pomalidomide.

    Pomalyst Adverse Reactions

    Adverse Reactions

    Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infections, back pain, pyrexia, rash, elevated creatinine, glucose, or ALT, decreased hemoglobin, platelets, phosphate, albumin, or calcium; thrombocytopenia, hepatotoxicity, dizziness, confusion, neuropathy, pneumonia, tumor lysis syndrome, severe cutaneous or hypersensitivity reactions.

    Adverse Reactions

    Multiple myeloma

    Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.

    Kaposi sarcoma

    Most common adverse reactions including laboratory abnormalities (≥30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea.

     

    Pomalyst Clinical Trials

    Clinical Trials

    Multiple Myeloma  
    Trial 1 was a phase 2, multicenter, randomized open-label study in patients with relapsed multiple myeloma (MM) who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib. Patients were considered relapsed if they had achieved at least stable disease for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease. Patients were considered refractory if they experienced disease progression on or within 60 days of their last therapy. A total of 221 patients were randomized to receive pomalidomide alone or pomalidomide with Low-dose Dex. In Trial 1, the safety and efficacy of pomalidomide 4 mg, once daily for 21 of 28 days, until disease progression, were evaluated alone and in combination with Low-dose Dex (40 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged 75 years or younger, or 20 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged greater than 75 years). Patients in the pomalidomide alone arm were allowed to add Low-dose Dex upon disease progression.

    The trial was designed to measure the number of patients whose cancer completely or partially disappeared after treatment (objective response rate, or ORR). The analysis results showed 7.4% (95% CI, 3.3-14.1) of patients treated with Pomalyst alone achieved ORR. In patients treated with Pomalyst plus low-dose dexamethasone, 29.2% (95% CI, 21-38.5) achieved ORR with a 7.4-month (95% CI, 5.1-9.2) median duration of response.

    Trial 2 was a Phase 3 multi-center, randomized, open-label study, where Pomalyst + Low-dose Dex therapy was compared to High-dose Dex in adult patients with relapsed and refractory MM, who had received at least two prior treatment regimens, including lenalidomide and bortezomib, and demonstrated disease progression on or within 60 days of the last therapy. A total of 455 patients were enrolled in the trial: 302 in the Pomalyst + Low-dose Dex arm and 153 in the High-dose Dex arm. Patients in the Pomalyst + Low-dose Dex arm were administered 4 mg Pomalyst orally on Days 1 to 21 of each 28-day cycle. Dexamethasone (40 mg) was administered once per day on Days 1, 8, 15 and 22 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. For the High-dose Dex arm, dexamethasone (40 mg) was administered once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. Treatment continued until patients had disease progression. 

    The primary endpoints assessed were progression free survival (PFS), overall response rate (ORR), and overall survival (OS), which were based on the evaluation by the Independent Review Adjudication Committee (IRAC). 

    Results showed that PFS was significantly longer with Pomalyst + Low-dose Dex versus High-dose Dex: HR 0.45 (95% CI, 0.35-0.59; P <0.001). OS was also significantly longer with Pomalyst + Low-dose Dex compared to High-dose Dex: HR 0.70 (95% CI, 0.54-0.92; P =0.009). In addition, the ORR was also higher with Pomalyst + Low-dose Dex compared to High-dose Dex (23.5% vs 3.9%), respectively.

    Kaposi Sarcoma 
    The clinical trial 12-C-0047 (NCT01495598), was an open label, single center, single arm clinical study that evaluated the safety and efficacy of Pomalyst in patients with Kaposi sarcoma (KS). A total of 28 patients (18 HIV-positive, 10 HIV-negative) received Pomalyst 5 mg orally once daily on Days 1 through 21 of each 28-day cycle until disease progression or unacceptable toxicity. All HIV-positive patients continued highly active antiretroviral therapy (HAART). Patients received thromboprophylaxis with aspirin 81 mg once daily throughout therapy. Seventy five percent of patients had advanced disease (T1) at the time of enrollment, 11% had ≥ 50 lesions, and 75% had received prior chemotherapy. The major efficacy outcome measure was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR), and partial response (PR). Response was assessed by the investigator according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for KS. The median time to first response was 1.8 months (0.9-7.6).

    Results showed an ORR of 71% (95% CI, 51-87) among all patients, with a median duration of response of 12.1 months (95% CI, 7.6-16.8). Among HIV-positive patients, the ORR was 67% (95% CI, 41-87), with a median duration of response of 12.5 months (95% CI, 6.5-24.9). An ORR of 80% (95% CI, 44-98) was observed among HIV-negative patients, with a median duration of response of 10.5 months (95% CI, 3.9-24.2). 

    Pomalyst Note

    Notes

    Available only through Pomalyst REMS program. More information about the Pomalyst REMS program is available at www.celgeneriskmanagement.com or call (888) 423-5436.

    Pomalyst Patient Counseling

    Patient Counseling

    Embryo-Fetal Toxicity 
    Advise patients that pomalidomide is contraindicated in pregnancy. Pomalidomide is a thalidomide analogue and may cause serious birth defects or death to a developing baby.

    • Advise females of reproductive potential that they must avoid pregnancy while taking Pomalidomide and for at least 4 weeks after completing therapy.  
    • Initiate pomalidomide treatment in females of reproductive potential only following a negative pregnancy test.
    • Advise females of reproductive potential of the importance of monthly pregnancy tests and the need to use 2 different forms of contraception, including at least 1 highly effective form, simultaneously during pomalidomide therapy, during dose interruptions, and for 4 weeks after she has completely finished taking pomalidomide. Highly effective forms of contraception other than tubal ligation include IUD and hormonal (birth control pills, injections, patch, or implants) and a partner’s vasectomy. Additional effective contraceptive methods include latex or synthetic condom, diaphragm, and cervical cap.
    • Instruct patient to immediately stop taking pomalidomide and contact her healthcare provider if she becomes pregnant while taking this drug, if she misses her menstrual period or experiences unusual menstrual bleeding, if she stops taking birth control, or if she thinks FOR ANY REASON that she may be pregnant.
    • Advise males to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide and for up to 4 weeks after discontinuing pomalidomide, even if they have undergone a successful vasectomy.
    • Advise male patients taking pomalidomide that they must not donate sperm.
    • All patients must be instructed to not donate blood while taking pomalidomide and for 4 weeks following discontinuation of pomalidomide.

    Venous and Arterial Thromboembolism 

    Inform patients of the risk of developing DVT, PE, MI, and stroke and to report immediately any signs and symptoms suggestive of these events for evaluation.

    Hematologic Toxicities 

    Inform patients on the risks of developing neutropenia, thrombocytopenia, and anemia and the need to report signs and symptoms associated with these events to their healthcare provider for further evaluation.

    Hepatotoxicity 

    Inform patients on the risks of developing hepatotoxicity, including hepatic failure and death, and to report signs and symptoms associated with these events to their healthcare provider for evaluation.

    Severe Cutaneous Reactions 

    Inform patients of the potential risk for severe skin reactions such as SJS, TEN and DRESS and to report any signs and symptoms associated with these reactions to their healthcare provider for evaluation.

    Dizziness and Confusional State 

    Inform patients of the potential risk of dizziness and confusional state with the drug, to avoid situations where dizziness or confusional state may be a problem, and not to take other medications that may cause dizziness or confusional state without adequate medical advice.

    Neuropathy 

    Inform patients of the risk of neuropathy and to report the signs and symptoms associated with these events to their healthcare provider for further evaluation.

    Second Primary Malignancies 

    Inform the patient that the potential risk of developing acute myelogenous leukemia during treatment with pomalidomide is unknown.

    Tumor Lysis Syndrome 

    Inform patients of the potential risk of tumor lysis syndrome and to report any signs and symptoms associated with this event to their healthcare provider for evaluation.

    Hypersensitivity 

    Inform patients of the potential for severe hypersensitivity reactions such as angioedema and anaphylaxis to pomalidomide. Instruct patients to contact their healthcare provider right away for any signs and symptoms of these reactions. Advise patients to seek emergency medical attention for signs or symptoms of severe hypersensitivity reactions.

    Smoking Tobacco 

    Advise patients that smoking tobacco may reduce the efficacy of pomalidomide.

    Cost Savings Program

    The Pomalyst savings program is available here.

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