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POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

IN PATIENTS WHO RECEIVED REVLIMID® (lenalidomide) AND A PI

Proven OS benefit vs high-dose dex.1

(Secondary endpoint)

POMALYST + dex prolonged median overall survival vs high-dose dex in the doublet Phase 3 trial.1

POMALYST® + dexamethasone Overall Survival ITT Population Data

In the Phase 3 trial, OS was based on the assessment by the Independent Review Adjudication Committee (IRAC) review at the final OS analysis.

POMALYST + low-dose dex significantly prolonged median progression-free survival vs high-dose dex.1

POMALYST + low-dose dex doubled the median PFS of high-dose dex (primary endpoint)1

  • Median PFS was significantly longer with POMALYST + low-dose dex vs high-dose dex (3.6 vs 1.8 months; HR 0.45; 95% Cl 0.35; 0.59; P<0.001)
POMALYST® + dexamethasone Median Progression-Free Survival Data

In the Phase 3 trial, PFS was based on the assessment by the IRAC review at the final PFS analysis.1

An expert overview of clinical data.

 

Vimeo ID: 207128961

Watch expert Dr. Joshua Richter provide an in-depth clinical overview of the POMALYST doublet Phase 3 clinical trial.


View Video Transcript

Hello. My name is Dr. Joshua Richter. I specialize in the treatment of multiple myeloma.

Today, I’ll be speaking with you about POMALYST® (pomalidomide), a therapy for patients with relapsed and refractory multiple myeloma. I will be reviewing some of the important data demonstrating that POMALYST® plus low-dose dexamethasone is the only proven treatment to significantly prolong overall survival in patients who have failed REVLIMID® (lenalidomide) and bortezomib.

But before we begin, let’s go over the full indication and some important safety information for POMALYST.

POMALYST® is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of their last therapy.

POMALYST has the following Boxed WARNINGS:
EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

  • POMALYST is contraindicated in pregnancy. POMALYST 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 POMALYST treatment.
  • Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.

POMALYST is only available through a restricted distribution program called POMALYST REMS®.

Venous and Arterial Thromboembolism

  • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. 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.

 

This presentation will review a variety of topics related to POMALYST, such as:

  • Challenges in relapsed/refractory multiple myeloma
  • Phase 3 trial design and results, including overall survival data for POMALYST
  • Dosing and administration of POMALYST, including patients with all levels of renal Impairment

Please note the important pregnancy contraindication shown here, and other important safety information for POMALYST throughout the presentation. We’ll review the Important Safety Information in full at the end of the presentation.

I’ll start with a brief overview of relapsed/refractory multiple myeloma and the clinical challenges we continue to face.

While there has been significant progress in multiple myeloma treatment, myeloma remains an incurable disease.1,2

It is characterized by periods of response, remission, and multiple relapses.1 These relapses are largely due to the inability to completely eradicate residual myeloma cells.2-4

Because patients experience multiple relapses, the prognosis for relapsed and refractory disease is relatively poor.4

Overall survival decreases with each successive treatment regimen, and median overall survival for these patients can range from as little as 6 to 9 months.4,5

Patients with relapsed/refractory disease remain difficult to treat given that they are typically symptomatic, have potential comorbidities, and have characteristically resistant disease.4

Although these patients are challenging to treat, there are therapies such as POMALYST that can help. I’ll begin by explaining how POMALYST works in this setting.

POMALYST is an IMiD that has a multifaceted mechanism of action. It exhibits tumoricidal activity by inhibiting the proliferation of myeloma cell lines that acquire resistance to REVLIMID.

Additionally, pomalidomide demonstrates synergy with dex in both REVLIMID-sensitive and REVLIMID- resistant myeloma cell lines to induce tumor cell apoptosis.

Pomalidomide has immunomodulatory properties. It enhances T cell- and natural killer cell-mediated immunity and inhibits production of pro-inflammatory cytokines such as TNF-α and IL-6.

Pomalidomide has also demonstrated antiangiogenic activity in cellular and animal models.

Now that we have a general understanding of how POMALYST works, it’s important to be aware of some of its warnings and precautions.

Embryo-fetal toxicity: Females of reproductive potential should be advised according to the Boxed WARNING shown earlier in this presentation. Male patients are advised to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm. Patients taking POMALYST must not donate blood while on treatment or for 4 weeks after discontinuation. Please refer to the full Important Safety Information at the end of this presentation.

Next we will be discussing a pivotal Phase 3 clinical trial that evaluated POMALYST in patients with relapsed and refractory multiple myeloma.

POMALYST plus low-dose dex was compared to high-dose dex in adult patients who received at least two prior regimens, including REVLIMID and bortezomib. These patients also demonstrated disease progression on or within 60 days of the last therapy. The primary endpoint of the study was progression-free survival, and overall survival was a key secondary endpoint.6

A total of 455 patients were enrolled in the study.

Patients in the POMALYST plus low-dose dex arm were administered 4 mg of POMALYST orally on Days 1 through 21 of each 28-day cycle. Low-dose dex was administered once per day on Days 1, 8, 15, and 22 of the 28-day cycle. Patients over 75 years of age started treatment with 20 mg of dex, using the same schedule.

In the comparator arm, high-dose dex was administered at 40 mg dosed once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle. Patients older than 75 started treatment with 20 mg of dex using the same schedule.

Patients receiving POMALYST were required to receive prophylaxis or antithrombotic treatment, as well as other patients with a history of DVT or PE.

It’s important to note that treatment continued until patients had disease progression.

The baseline characteristics of the patients in the trial were well balanced between both arms. The majority of patients were refractory to REVLIMID and/or bortezomib.

As previously stated, progression-free survival was the primary endpoint, and overall survival was a key secondary endpoint in the Phase 3 trial.

As evident by the Kaplan-Meier analysis, POMALYST plus low-dose dex prolonged overall survival vs high-dose dex.

The difference in overall survival between POMALYST plus low-dose dex vs high-dose dex was statistically significant, with a 30% reduced risk of death vs high-dose dex.

Patients who received POMALYST plus low-dose dex achieved a 12.4-month median overall survival.

I’d like to point out that 53% of patients in the high-dose dex arm subsequently received POMALYST as rescue therapy. In the final analysis, patients who switched arms and received POMALYST were reported as part of the high-dose dex arm.

Patients taking POMALYST are at increased risk for venous and arterial thromboembolism, as noted in the Boxed WARNING shown earlier in this presentation, so it’s important to minimize other modifiable factors such as hyperlipidemia, hypertension, and smoking.

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

In addition to overall survival, POMALYST plus low-dose dex also delivered significantly longer progression-free survival and provided a 55% reduced risk of progression or death vs high-dose dex.

Median progression-free survival for POMALYST plus low-dose dex was 3.6 months, while the median progression-free survival for high-dose dex was 1.8 months.

Based on these survival data, POMALYST is a treatment option for patients who have progressed on REVLIMID and a proteasome inhibitor. Note that 74% of patients in the study were refractory to both REVLIMID and bortezomib.

Patients taking POMALYST are at an increased risk of hematologic toxicities, such as neutropenia, anemia, and thrombocytopenia. Neutropenia was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials.

Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST.

Patients receiving POMALYST also have an increased risk for developing severe cutaneous reactions, including hypersensitivity reactions. Angioedema and severe cutaneous reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms, have been reported, and POMALYST should be discontinued if any of these occur.

In the next part of the presentation, I’ll discuss safety data, and explain how POMALYST should be dosed.

Overall, the safety profile for POMALYST is well established.

In the Phase 3 trial, nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). Shown here are the most common adverse reactions observed in the POMALYST plus low-dose dex treatment arm, including neutropenia, fatigue and asthenia, upper respiratory tract infection, thrombocytopenia, pyrexia, dyspnea, diarrhea, and constipation.

Additional adverse reactions and their frequencies are shown on the screen.

The recommended starting dose for most patients is 4 mg once daily orally on Days 1-21 of repeated 28-day cycles.

POMALYST should always be given in combination with dex, and treatment should be continued until disease progression.

POMALYST is available in 4 dosage strengths, which may help keep your patients on therapy.

Here are some important dosing guidelines for POMALYST:

POMALYST should be given in combination with dexamethasone.

POMALYST may be taken with water, and with or without food.

Inform patients not to break, chew, or open the capsules.

Monitor CBCs every week for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.

Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes and evaluate. After returning to baseline values, treatment at a lower dose may be considered.

In addition, POMALYST should not be used concomitantly with strong CYP1A2 inhibitors. Please review the drug interaction information here, and refer to the full Important Safety Information at the end of the presentation.

POMALYST does not generally require a starting dose reduction for patients with renal impairment, unless they’re on dialysis.

For patients with mild, moderate, or severe renal impairment who are not on dialysis, a 4 mg starting dose is recommended. For patients with severe renal impairment on dialysis, the recommended starting dose is 3 mg.

On dialysis days, it’s important that the patient take POMALYST following hemodialysis.

Please refer to the full Important Safety Information at the end of the presentation for guidance on the use of POMALYST in this and other specific populations.

Dose modifications may be needed for some of your patients because of other adverse reactions. In the Phase 3 trial, 67 percent of patients experienced dose interruption, while 27 percent experienced dose reduction.

8% of patients discontinued POMALYST due to treatment-related adverse reactions.

Now we will discuss some more specific dose modifications for your patients with hematologic toxicities such as neutropenia and/or thrombocytopenia. It’s important to monitor patients for hematologic toxicities by obtaining complete blood counts weekly for the first 8 weeks and monthly thereafter.

In the event of neutropenia, when the absolute neutrophil count, or “ANC,” is less than 500 per mcL, interrupt POMALYST treatment and follow the CBC weekly.

When the ANC returns to at least 500 per mcL, resume POMALYST at 3 mg daily.

For each subsequent drop below 500 per mcL, interrupt POMALYST treatment.

When the ANC returns to at least 500 per mcL, resume POMALYST at 1 mg less than the previous dose.

Remember, to initiate a subsequent cycle of POMALYST, the neutrophil count must be at least 500 per mcL.

For patients with thrombocytopenia, when platelets are less than 25,000 per mcL, interrupt POMALYST treatment and follow the CBC weekly.

When platelets return to at least 50,000 per mcL, resume POMALYST at 3 mg daily.

For each subsequent drop below 25,000 per mcL, interrupt POMALYST treatment.

When platelets return to at least 50,000 per mcL, resume POMALYST at 1 mg less than the previous dose.

To initiate a subsequent cycle of POMALYST, the platelet count must be at least 50,000 per mcL.

Dose modifications of POMALYST should be performed in the event of Grade 3 or 4 thrombocytopenia.

For other Grade 3 or 4 toxicities, hold treatment and restart treatment at 1 mg less than the previous dose when the toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion.

Permanently discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reaction.

Safety is an important part of any treatment, so I will summarize the Risk Evaluation and Mitigation Strategy for POMALYST, also referred to as POMALYST REMS.

Because of the embryo-fetal risk, POMALYST is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called “POMALYST REMS®.”

Required components of the POMALYST REMS program include the following:

Prescribers must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements.

Patients must sign a Patient-Physician Agreement Form and comply with the REMS requirements. In particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements, and males must comply with the contraception requirements.

Pharmacies must be certified with the POMALYST REMS program, must only dispense to patients who are authorized to receive POMALYST, and comply with REMS requirements.

Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.

If you would like to learn more about the benefits and risks of POMALYST, visit POMALYST.com or reach out to your local Celgene representative.

Finally, let’s review the Important Safety Information for POMALYST.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

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

POMALYST is only available through a restricted distribution program called POMALYST REMS®.

Venous and Arterial Thromboembolism

  • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. 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.

 

CONTRAINDICATIONS

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

WARNINGS AND PRECAUTIONS

  • Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS
  • Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy.

Males must not donate sperm.

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

  • POMALYST REMS® Program: See Boxed WARNINGS

– Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive POMALYST. 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.

– Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.

  • 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 (for example, hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.
  • 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.
  • Hematologic Toxicity: Neutropenia (46%) was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.
  • Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
  • 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. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe cutaneous reactions such as SJS, TEN or DRESS, and do not resume therapy.
  • Dizziness and Confusional State: In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients 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: In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
  • Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
  • Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

ADVERSE REACTIONS

The most common adverse reactions for POMALYST (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upperrespiratory tract infections, back pain, and pyrexia.

In the phase III trial, nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). Adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than control) included neutropenia (51.3%), fatigue and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the POMALYST+ low-dose dex arm and ≥1% higher than control) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

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 POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST 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 pomalidomide in human milk, the effects of POMALYST on the breastfed child, or the effects of POMALYST 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 POMALYST, advise women not to breastfeed during treatment with POMALYST.
  • Pediatric Use: Safety and effectiveness have not been established in pediatric patients.
  • Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience pneumonia.
  • Renal Impairment: Reduce POMALYST dose by 25% in patients with severe renal impairment requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.
  • Hepatic Impairment: Reduce POMALYST dose by 25% in patients with mild to moderate hepatic impairment and 50% in patients with severe hepatic impairment.
  • Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

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

Thank you. That concludes our discussion of POMALYST for the treatment of relapsed and refractory multiple myeloma patients.

  1. Hajek R, ed. Multiple Myeloma — A Quick Reflection on the Fast Progress. InTech; 2013.
  1. Hart AJ, Jagasia MH, Kim SA, et al. Minimal residual disease in myeloma — are we there yet? Biol Blood Marrow Transplant. 2012;18(12):1790-1799.
  1. Kyle RA, Rajkumar SV. Multiple myeloma. Clinical course of patients with relapsed multiple myeloma. N Engl J Med. 2004;351(18):1860-1873.
  1. Richardson P, Mitsiades C, Schlossman R, et al. The treatment of relapsed and refractory multiple myeloma. Hematology Am Soc Hematol Educ Program. 2007;(1): 317-323.
  1. Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867-874.
  1. San Miguel J, Weisel K, Moreau P, Lacy M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(11):1055-1066.

CI, confidence interval; HR, hazard ratio; IRAC, Independent Review Adjudication Committee; ITT, intent-to-treat; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor.

POMALYST + dex has a
well-established safety profile.1

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

  • POMALYST is contraindicated in pregnancy. POMALYST 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 POMALYST treatment.
  • Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.

POMALYST is only available through a restricted distribution program called POMALYST REMS®.

Venous and Arterial Thromboembolism

  • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. 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.

CONTRAINDICATIONS FOR POMALYST

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

CONTRAINDICATIONS FOR DARATUMUMAB

  • Daratumumab is contraindicated in patients with a history of severe hypersensitivity (e.g. anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS FOR POMALYST

  • Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS
    • Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm.
    • Blood Donation: Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation of POMALYST therapy because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST.
  • POMALYST REMS Program: See Boxed WARNINGS
    • Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive POMALYST. 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.
    • Further information about the POMALYST REMS program is available at CelgeneRiskManagement.com or by telephone at 1-888-423-5436.
  • 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 (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.
  • 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.
  • Hematologic Toxicity: Neutropenia (46%) was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.
  • Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
  • 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. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe cutaneous reactions such as SJS, TEN or DRESS, and do not resume therapy.
  • Dizziness and Confusional State: In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients 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: In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
  • Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
  • Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

WARNINGS AND PRECAUTIONS FOR DARATUMUMAB

  • Infusion reactions: Interrupt daratumumab infusion for infusion reactions of any severity. Permanently discontinue the infusion in case of anaphylactic reactions or life-threatening infusion reactions and institute appropriate emergency care.
  • Interference with cross-matching and red blood cell antibody screening: Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test), which may persist for up to 6 months after the last daratumumab infusion. Type and screen patients prior to starting treatment. Inform blood banks that a patient has received daratumumab.
  • Neutropenia: Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. Dose delay may be required to allow recovery of neutrophils.
  • Thrombocytopenia: Monitor complete blood cell counts periodically during treatment. Dose delay may be required to allow recovery of platelets.
  • Interference with Determination of Complete Response: Daratumumab can interfere with the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

 

WARNINGS AND PRECAUTIONS FOR ELOTUZUMAB

  • Infusion Reactions: Premedication is required. Interrupt elotuzumab for Grade 2 or higher and permanently discontinue for severe infusion reaction.
  • Infections: Monitor for fever and other signs of infection and treat promptly.
  • Second Primary Malignancies (SPM): Higher incidences of SPM were observed in a controlled clinical trial of patients with multiple myeloma receiving elotuzumab.
  • Hepatotoxicity: Monitor liver function and stop elotuzumab if hepatotoxicity is suspected.
  • Interference with Determination of Complete Response: Elotuzumab can interfere with assays used to monitor M-protein. This interference can impact the determination of complete response.

ADVERSE REACTIONS FOR POMALYST + dexamethasone

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

In the phase III trial, nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). Adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than control) included neutropenia (51.3%), fatigue and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥1% higher than control) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

 

ADVERSE REACTIONS FOR POMALYST + dexamethasone + daratumumab

The most common adverse reactions (≥20%) included neutropenia (95%), lymphopenia (94%), thrombocytopenia (75%), anemia (57%), infusion reactions (50%), fatigue (50%), upper respiratory tract infection (50%), cough (43%), diarrhea (38%), constipation (33%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), back pain (25%), insomnia (23%), arthralgia (22%), vomiting (21%), dizziness (21%), and chills (20%).  Grade 3 or 4 hematology laboratory abnormalities included: neutropenia (82%), lymphopenia (71%), anemia (30%), and thrombocytopenia (20%).

 

ADVERSE REACTIONS FOR POMALYST + dexamethasone + elotuzumab

Adverse reactions (≥15% for Pd + elotuzumab and ≥5% higher than Pd) included constipation (22%, 11%), hyperglycemia (20%, 15%), pneumonia (18%, 13%), diarrhea (18%, 9%), respiratory tract infection (17%, 9%), bone pain (15%, 9%), and dyspnea (15%, 7%). Laboratory abnormalities worsening from baseline (≥20% for Pd + elotuzumab and ≥5% higher than Pd; criteria met for All Grades or Grade 3/4) included lymphopenia (98%, 91%), leukopenia (80%, 87%), thrombocytopenia (78%, 73%), hypoalbuminemia (65%, 56%), hypocalcemia (58%, 40%), hyperglycemia (40%, 25%), hyponatremia (40%, 18%), and hypokalemia (23%, 16%). Vital sign abnormalities (≥20% for Pd + elotuzumab vs. Pd) included heart rate <60 bpm (43%, 22%) and heart rate ≥100 bpm (23%, 24%). Grade 3 or 4 laboratory abnormalities worsening from baseline (≥20% for Pd + elotuzumab and ≥5% higher than Pd; criteria met for All Grades or Grade 3/4) included lymphopenia (70%, 35%), leukopenia (52%, 35%), and thrombocytopenia (17%, 20%).

 

DRUG INTERACTIONS FOR POMALYST

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS FOR POMALYST

  • 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 POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST 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 pomalidomide in human milk, the effects of POMALYST on the breastfed child, or the effects of POMALYST 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 POMALYST, advise women not to breastfeed during treatment with POMALYST.
  • Pediatric Use: Safety and effectiveness have not been established in pediatric patients.
  • Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience pneumonia.
  • Renal Impairment: Reduce POMALYST dose by 25% in patients with severe renal impairment requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.
  • Hepatic Impairment: Reduce POMALYST dose by 25% in patients with mild to moderate hepatic impairment and 50% in patients with severe hepatic impairment.
  • Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

Please see full Prescribing Information for POMALYST, including Boxed WARNINGS. 

Information about POMALYST + dexamethasone + daratumumab and POMALYST + dexamethasone + elotuzumab does not appear in the POMALYST Prescribing Information (PI). Please see the daratumumab and elotuzumab full PI for a complete discussion of Important Safety Information at www.darzalex.com and www.empliciti.com, respectively.