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POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for adult 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.

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Hear peer and expert perspectives on the use of POMALYST in the treatment of relapsed/refractory multiple myeloma in patients who received REVLIMID® (lenalidomide)* and a PI.

 

Dr. Jeffrey Matous shares his insights about a triplet combination with POMALYST.

Dr. Jeffrey Matous, Colorado Blood Cancer Institute

View Video Transcript

My name is Dr. Jeff Matous. I’m from the Colorado Blood Cancer Institute in Denver, and I see many patients with multiple myeloma every day. The treatment landscape for myeloma has evolved rapidly in the past few years. Because of that, it’s important for me and the medical community to stay up-to-date on currently approved therapy options that may benefit our patients.

One of those treatments I use as a foundational therapy is POMALYST, either as part of a doublet regimen in combination with dexamethasone or as a triplet regimen with dexamethasone and daratumumab for patients who have received prior lenalidomide and a proteasome inhibitor.

Before we review the efficacy and safety data for a POMALYST-based triplet regimen, let’s review some Important Safety Information for POMALYST.

POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for adult 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.

POMALYST + dexamethasone + daratumumab is indicated for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

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

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.

Please see important safety information throughout this video and full prescribing information for POMALYST, including Boxed WARNINGS.

POMALYST was studied in a Phase 3, multicenter, randomized, open-label trial of POMALYST + low-dose dexamethasone vs high-dose dexamethasone in patients with relapsed/refractory multiple myeloma who had received at least 2 prior treatment regimens, including REVLIMID (generic name lenalidomide) and bortezomib, and demonstrated disease progression on or within 60 days from the last therapy. A total of 455 patients were enrolled in the study.

Some key exclusion criteria included serum bilirubin greater than 2.0 mg/dL, AST/ALT greater than 3.0 times the upper limit of normal, and CrCl less than 45 mL/min.

The primary endpoint was progression-free survival, or PFS. A secondary endpoint was overall survival, or OS. Treatment continued until disease progression.

Patients in the POMALYST + low-dose dexamethasone arm received 4 mg of POMALYST orally on Days 1 to 21 of 28-day cycles with 40 mg of dexamethasone once daily on specified days in the cycle, as seen here. Patients in the high-dose dexamethasone arm received 40 mg of dexamethasone once daily on specified days in each 28-day cycle, as seen here.

Patients older than 75 years of age received 20 mg of dexamethasone, with the same respective dosing schedules.

Patients receiving POMALYST, as well as any other patient with a history of deep venous thrombosis or pulmonary embolism, were required to receive prophylaxis or antithrombotic treatment.

In the study, the majority of patients were refractory to REVLIMID, bortezomib, or both.

Study results demonstrated a 30% reduced risk of death for POMALYST + low-dose dexamethasone vs high-dose dexamethasone. The median OS for POMALYST + low-dose dexamethasone was 12.4 months vs 8.0 months for high-dose dexamethasone.

For the primary endpoint, POMALYST + low-dose dexamethasone doubled the median PFS of high-dose dexamethasone (3.6 vs 1.8 months).

Recently, there was a study proving the safety and efficacy of a POMALYST-based triplet regimen in patients with relapsed/refractory myeloma.

POMALYST + low-dose dexamethasone was studied in combination with daratumumab in a trial of 103 patients without a comparator arm. This trial led to the FDA approval of this POMALYST-based triplet regimen.

The median patient age in the trial was 64 years, and all of the patients enrolled had previously received REVLIMID.

89% of the patients enrolled in the trial were refractory to REVLIMID, while 71% were refractory to bortezomib, and 64% of patients were refractory to both REVLIMID and bortezomib.

Patients received 4 mg of POMALYST once daily for Days 1-21 during a repeated 28-day cycle in combination with 40 mg of low-dose oral or intravenous dexamethasone per week.

In addition to POMALYST and low-dose dexamethasone, patients received 16 mg/kg of daratumumab as an infusion based on the schedule shown on screen.

On days with a daratumumab infusion, patients received 20 mg of dexamethasone as a pre-infusion medication, with the rest administered the day after the daratumumab infusion. Additional information on reduced doses of dexamethasone is shown at the bottom of the screen.

Patients in the trial were treated until disease progression.

Now that we’ve reviewed the study design and dosing information, let’s dive into the efficacy results and safety profile for POMALYST + low-dose dexamethasone in combination with daratumumab.

59% of patients studied in the trial achieved a response with POMALYST + low-dose dexamethasone in combination with daratumumab, with 42% reaching a very good partial response or better.

The median time to response was 1 month, while the median duration of response was 13.6 months.

Patients in the study were treated for a median of 6 months, and 13% of these patients discontinued treatment due to adverse reactions.

Shown here are the adverse reactions of any grade that occurred in more than 20% of patients treated with POMALYST + low-dose dexamethasone in combination with daratumumab. The most common adverse reactions occurring in at least 50% of patients were neutropenia, lymphopenia, thrombocytopenia, anemia, infusion reactions, fatigue, and upper respiratory tract infection. Grade 3/4 hematologic adverse reactions that occurred in at least 20% of patients are also shown at the bottom of the screen.

The overall incidence of adverse reactions was 49%. Serious adverse reactions reported in ≥5% of patients included pneumonia, which occurred in 7% of patients.

There are certain Warnings and Precautions to keep in mind when using daratumumab, including:

  • Infusion reactions,
  • Interference with cross-matching and red blood cell antibody screening,
  • Neutropenia,
  • Thrombocytopenia,
  • And interference with determination of complete response

We’ll discuss more information about the Warnings and Precautions for this regimen later on in this presentation.

The results of this trial show that POMALYST + low-dose dexamethasone in combination with daratumumab is a treatment option for patients who are refractory to REVLIMID and who have received a prior proteasome inhibitor.

Some patients may not be a candidate for a triplet regimen. For those who are likely to benefit from a doublet, consider using POMALYST in combination with low-dose dexamethasone, an all-oral regimen for relapsed/refractory multiple myeloma.

To learn more about the overall survival and safety data from the Phase 3 trial for POMALYST + low-dose dexamethasone, please visit Pomalyst.com.

The results of both POMALYST plus low-dose dexamethasone and POMALYST plus dexamethasone in combination with daratumumab support the use of POMALYST as a therapy in patients with relapsed/refractory multiple myeloma who have received prior lenalidomide and a proteasome inhibitor.

Now, let’s review some Important Safety Information for POMALYST.

POMALYST has boxed warnings for embryo-fetal toxicity and venous and arterial thromboembolism.

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 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.
  • Hypersensitivity: POMALYST is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any of the excipients.

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 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 (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: Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These reactions can be fatal. Consider POMALYST interruption or discontinuation for Grade 2-3 skin rash. Permanently discontinue POMALYST for Grade 4 rash, exfoliative or bullous rash, or any other severe cutaneous reactions such as SJS, TEN or DRESS.
  • 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.
  • Hypersensitivity: Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to POMALYST have been reported. Permanently discontinue POMALYST for angioedema or anaphylaxis.

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.

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%).

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 Important Safety Information throughout this video and full Prescribing Information for POMALYST, including Boxed WARNINGS.

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

I hope you have found the information in this video valuable. As a reminder, please visit POMALYST.com for more information or contact your local Celgene representative.

References

1. POMALYST [package insert]. Summit, NJ: Celgene Corp.
2. Data on file. Bristol-Myers Squibb Co; 2018.
3. Daratumumab [package insert]. Horsham, PA: Janssen Biotech, Inc.

POMALYST®, POMALYST REMS®, and REVLIMID®, and associated logos are trademarks of Celgene Corporation, a Bristol Myers Squibb company.

Other trademarks are property of their respective owners.

© 2020 Bristol-Myers Squibb Company. 07/20 US-POM-20-0242

Dr. Ken Shain provides his perspective on the use of combinations with POMALYST in the treatment of RRMM patients who have progressed on REVLIMID.

Combination regimen for relapsed/refractory multiple myeloma

View Video Transcript

I’m Doctor Ken Shain, and I specialize in the treatment of relapsed/refractory multiple myeloma at Moffitt Cancer Center.

Multiple myeloma has an exciting and dynamic treatment landscape, as options have evolved over the past several years.

I believe IMiD® agents are important options in multiple myeloma. In the relapsed and refractory setting, regimens that include POMALYST have demonstrated effectiveness in lenalidomide-refractory patients who have also received proteasome inhibitors. Patients who have been exposed to lenalidomide in earlier lines of therapy are a growing and clinically relevant population in multiple myeloma.

Today we’ll review a POMALYST doublet and triplet regimen. Studies demonstrated the efficacy and safety of POMALYST in these regimens, which led to 2 FDA approvals for patients with relapsed/refractory multiple myeloma who previously received REVLIMID or lenalidomide and a proteasome inhibitor.

Now let’s go over the Indications and some Important Safety Information for POMALYST.

POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for adult 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.

EMPLICITI® (elotuzumab) is indicated in combination with POMALYST and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

POMALYST carries Boxed WARNINGS for 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.

Please see Important Safety Information throughout this video and full Prescribing Information for POMALYST, including Boxed WARNINGS, at www.POMALYSTHCP.com and full Prescribing Information for EMPLICITI at www.EMPLICITIHCP.com.

POMALYST was studied in a Phase 3, multicenter, randomized, open-label trial of POMALYST + low-dose dexamethasone vs high-dose dexamethasone in patients with relapsed/refractory multiple myeloma who had received at least 2 prior treatment regimens, including REVLIMID (generic name lenolidomide) and bortezomib, and demonstrated disease progression on or within 60 days from the last therapy. A total of 455 patients were enrolled in the study.

Some key inclusion criteria included serum bilirubin greater than 2.0 mg/dL, AST/ALT greater than 3.0 times the upper limit of normal, and CrCl less than 45 mL/min.

The primary endpoint was progression-free survival, or PFS. A secondary endpoint was overall survival, or OS. Treatment continued until disease progression.

Patients in the POMALYST + low-dose dexamethasone arm received 4 mg of POMALYST orally on Days 1 to 21 of 28-day cycles with 40 mg of dexamethasone once daily on specified days in the cycle, as seen here Patients in the high-dose dexamethasone arm received 40 mg of dexamethasone once daily on specified days in each 28-day cycle, as seen here.

Patients older than 75 years of age received 20 mg of dexamethasone, with the same respective dosing schedules.

Patients receiving POMALYST, as well as any other patient with a history of deep venous thrombosis or pulmonary embolism, were required to receive prophylaxis or antithrombotic treatment.

In the study, the majority of patients were refractory to REVLIMID, bortezomib, or both.

Study results demonstrated a 30% reduced risk of death for POMALYST + low-dose dexamethasone vs high-dose dexamethasone. The median OS for POMALYST + low-dose dexamethasone was 12.4 months vs 8.0 months for high-dose dexamethasone.

For the primary endpoint, POMALYST + low-dose dexamethasone doubled the median PFS of high-dose dexamethasone (3.6 vs 1.8 months).

Now let’s review the triplet regimen of POMALYST plus dexamethasone and elotuzumab.

POMALYST plus dexamethasone and elotuzumab was studied in a Phase 2 trial known as ELOQUENT-3, which was published in The New England Journal of Medicine.

This Phase 2, randomized, open-label study evaluated 117 patients with relapsed/refractory multiple myeloma who have received at least 2 prior lines of therapy, including REVLIMID and a proteasome inhibitor, and were refractory to their most recent therapy. Patients were randomized to receive either the triplet regimen or the doublet. The primary endpoint was PFS, and secondary endpoints were overall response rate, or ORR, and OS, all of which were investigator-assessed.

Patients in the trial were treated until disease progression or unacceptable toxicity.

In the triplet arm, patients received 4 mg of POMALYST orally once daily on Days 1 to 21 of a repeated 28-day cycle. They also received dexamethasone and elotuzumab at these doses in Cycles 1 and 2, followed by these doses from Cycle 3 onward.

Prior to elotuzumab infusion, premedication with dexamethasone, antihistamines including H1 and H2 blockers, and acetaminophen was required.

At the bottom of the screen, you will see additional information about the administration of dexamethasone.

In the doublet arm, patients received POMALYST plus an oral 40-mg dose of dexamethasone weekly.

The majority of the patients (87%) were refractory to REVLIMID.

80% were refractory to a proteasome inhibitor, and 70% were refractory to both.

Let’s take a closer look at the efficacy results for POMALYST, dexamethasone, and elotuzumab.

The triplet regimen demonstrated statistically significant improvement in PFS versus the doublet, with a median PFS of 10.3 months versus 4.7 months.

This represents a 46% reduction in the risk of disease progression or death.

Patients in the study were treated for a median of 9 cycles for POMALYST plus dexamethasone and elotuzumab versus 5 cycles for POMALYST plus dexamethasone, with a minimum follow-up of 9.1 months.

Moving on to the response data, 53.3% of patients responded to POMALYST plus dexamethasone and elotuzumab compared with 26.3% of patients who responded to POMALYST plus dexamethasone. You can see how those overall rates break down into complete response, very good partial response, and partial response.

Now, let’s look at the safety profile for POMALYST plus dexamethasone and elotuzumab compared with POMALYST plus dexamethasone alone.

The most common adverse reactions of any grade that occurred in at least 20% of patients in the triplet arm and with at least a 5% higher incidence than the doublet arm were constipation and hyperglycemia.

Additional information on laboratory abnormalities worsening from baseline and vital sign abnormalities are also shown in this table.

The overall incidence of serious adverse reactions was 22% in patients treated with POMALYST plus dexamethasone and elotuzumab, compared with 15% treated with POMALYST plus dexamethasone.

The most frequent serious adverse reactions were pneumonia (13% vs 11%) and respiratory tract infection (7% vs 3.6%) in the POMALYST plus dexamethasone and elotuzumab vs POMALYST plus dexamethasone arms, respectively.

Sixty-five percent of patients treated in either arm experienced infections of any grade. Grade 3/4 infections were reported in 13% of patients treated with the triplet vs 22% with the doublet. Infusion reactions were reported in 3.3% of patients treated with the triplet.

Five percent of patients discontinued treatment due to adverse reactions with POMALYST plus dexamethasone and elotuzumab, compared with 1.8% with POMALYST plus dexamethasone.

We just reviewed the efficacy and safety data of POMALYST plus dexamethasone and elotuzumab in patients with relapsed and refractory multiple myeloma.

Some patients may not be candidates for a triplet regimen. For those who are likely to benefit from doublet, consider using POMALYST in combination with low-dose dexamethasone, a proven all-oral regimen for REVLIMID refractory patients who have also received a proteasome inhibitor.

Now, let’s go over the Indications and Important Safety Information for POMALYST plus dexamethasone and elotuzumab.

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.

EMPLICITI® (elotuzumab) is indicated in combination with POMALYST and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

POMALYST carries Boxed WARNINGS for 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.

POMALYST has the following 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.
  • Hypersensitivity: POMALYST is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any of the excipients.

POMALYST and EMPLICITI carry the following warnings and precautions.

  • Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS for POMALYST
    • 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 (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.
    • In the ELOQUENT-2 trial (EMPLICITI + lenalidomide + dexamethasone vs lenalidomide + dexamethasone) (N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphate >2X the upper limit were 2.5% (EMPLICITI arm) vs. 0.6% (control arm). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values.
  • Infusion Reactions:
    • Infusion reactions were reported in 3.3% of patients treated with EMPLICITI in the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone (EPd) vs pomalidomide + dexamethasone (Pd)].
    • The only infusion reaction symptom was chest discomfort (2%), which was Grade 1. All the patients who experienced an infusion reaction had them during the first treatment cycle.
    • If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
    • Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen prior to EMPLICITI infusion.
  • Infections:
    • In the ELOQUENT-3 trial (N=115), infections were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3-4 infections were reported in 13% (EPd) and 22% (Pd). Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd).
    • Monitor patients for development of infections and treat promptly.
  • 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. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These reactions can be fatal. Consider POMALYST interruption or discontinuation for Grade 2-3 skin rash. Permanently discontinue POMALYST for Grade 4 rash, exfoliative or bullous rash, or any other severe cutaneous reactions such as SJS, TEN or DRESS.
  • 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 (SPMs):
    • Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
    • In the EMPLICITI ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and 1.8% (Pd).
    • Monitor patients for the development of SPMs.
  • 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.
  • Interference With Determination of Complete Response: EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
  • Hypersensitivity: Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to POMALYST have been reported. Permanently discontinue POMALYST for angioedema or anaphylaxis.

ADVERSE REACTIONS 

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 + lowdose dex arm and ≥1% higher than control) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

Serious adverse reactions in the EMPLICITI ELOQUENT-3 trial were 22% (EPd) and 15% (Pd). The most frequent serious adverse reactions in the EPd arm compared to the Pd arm were: pneumonia (13%, 11%) and respiratory tract infection (7%, 3.6%).

The most common adverse reactions in EPd arm (≥20% EPd) and Pd, respectively, were constipation (22%, 11%) and hyperglycemia (20%, 15%).

Drug interactions for POMALYST are as follows.

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg.

Use in specific populations is as follows.

  • 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.
  • Pregnancy and EMPLICITI Use: There are no available data on EMPLICITI use in pregnant women to inform a drug-associated risk of major defects and miscarriage.
  • Lactation: There is no information regarding the presence of pomalidomide or elotuzumab in human milk, the effects of POMALYST or EMPLICITI 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 or POMALYST in combination with EMPLICITI.
  • 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 this video, and full Prescribing Information for POMALYST, including Boxed WARNINGS, at www.POMALYSTHCP.com and full Prescribing Information for EMPLICITI at www.EMPLICITIHCP.com.

Thank you for your time in reviewing these important data for POMALYST. For more information, please visit the POMALYST website or contact your local POMALYST representative.

References

1. POMALYST [package insert]. Summit, NJ: Celgene Corp.

2. EMPLICITI [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.

3. Data on file. Bristol-Myers Squibb Co; 2018.

4. Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379:1811-1822.

5. Sun Z, Zheng F, Wu S, Liu Y, Guo H, Liu Y. Triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma: a meta-analysis of phase III randomized controlled trials. Crit Rev Oncol Hematol. 2017;113:249-255.

6. REVLIMID [package insert]. Summit, NJ: Celgene Corp.

7. Moreau P, Zamagni E, Mateos MV. Treatment of patients with multiple myeloma progressing on frontline-therapy with lenalidomide. Blood Cancer J. 2019;9(4):38-45.

POMALYST®, REVLIMID®, POMALYST REMS®, and associated logos are registered trademarks of Celgene Corporation, a Bristol Myers Squibb company.

EMPLICITI® is a trademark of Bristol-Myers Squibb Company.

© 2020 Bristol-Myers Squibb Company. 07/20 US-POM-20-0243

Mechanism of Action

Explore the mechanism of action of POMALYST.

POMALYST® (pomalidomide) mechanism of action

A closer look at the mechanism of action of POMALYST.


View Video Transcript

Pomalidomide is an immunomodulatory agent with antineoplastic activity [1].

Pomalidomide has been shown to have in vitro activity that overcomes lenalidomide resistance [1]. In addition to the immunomodulatory and antineoplastic activity, pomalidomide demonstrated antiangiogenicactivity in an in vitro umbilical cord model and in vivo [1,2].

The antineoplastic activity of pomalidomide has been established in in vitro cellular assays. Pomalidomide has been shown to inhibit proliferation and induce apoptosis of hematopoietic tumor cells [1].

Pomalidomide also inhibited the proliferation of lenalidomide-resistant multiple myeloma cell lines [1].

Pomalidomide synergized with dexamethasone and induced tumor cell apoptosis in both lenalidomide-resistant and lenalidomide-sensitive cell lines [1].

Pomalidomide has been shown to have immunomodulatory activity [1]. Pomalidomide enhanced T cell- and natural killer cell-mediated immunity [1].

It also inhibited production of proinflammatory cytokines, such as TNF-α and IL-6, by monocytes [1,2].

Pomalidomide also demonstrated antiangiogenic properties [1,2]. This activity is supported by an in vivo mouse tumor model and an in vitro umbilical cord model [1].

Pomalidomide is an immunomodulatory and antineoplastic agent with in vitro activity that overcomes lenalidomide resistance [1]. Based on pre-clinical findings, pomalidomide, in combination with low-dose dexamethasone, was evaluated in a Phase 3 multi-center, randomized, open-label study [1].

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Please see accompanying full Prescribing Information, including Boxed WARNINGS.

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References:

  1. POMALYST (pomalidomide) Capsules PI. 2015.
  2. Terpos E, Kanellias N, Christoulas D, et al. Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma. Onco Targets Ther. 2013;6:531-538.

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© 2015 Celgene Corporation 12/15 US-POM150057


*Please see full Prescribing Information, including Boxed WARNINGS, for REVLIMID.
Patients must have also received a proteasome inhibitor (PI).

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Indications for POMALYST® (pomalidomide) and EMPLICITI® (elotuzumab)
POMALYST is a thalidomide analogue indicated, in combination with dexamethasone, for adult 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.

EMPLICITI is indicated in combination with POMALYST and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor

Indications for POMALYST + dexamethasone + daratumumab

POMALYST + dexamethasone + daratumumab is indicated for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

Indications for POMALYST + dexamethasone + isatuximab-irfc

POMALYST + dexamethasone + isatuximab-irfc is indicated for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

Information about POMALYST + dex + daratumumab (dara), POMALYST + dex + EMPLICITI, and POMALYST + dex + isatuximab (isa) does not appear in the POMALYST full Prescribing Information. Please see the dara, EMPLICITI, and isa full Prescribing Information for a discussion of Important Safety Information at www.darzalex.com (dara), www.empliciti.com (EMPLICITI), and www.sarclisa.com, (isa).

Important Safety Information

POMALYST Boxed WARNINGS

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. 
  • Hypersensitivity: POMALYST is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any of the excipients.

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.

CONTRAINDICATIONS FOR ISATUXIMAB-IRFC

  • Isatuximab-irfc is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of the excipients.

WARNINGS AND PRECAUTIONS FOR POMALYST AND EMPLICITI® (elotuzumab)

  • Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS for POMALYST
    • 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 for POMALYST. 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.
    • In the ELOQUENT-2 trial (EMPLICITI + lenalidomide + dexamethasone vs lenalidomide + dexamethasone) N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphatase <2X the upper limit were 2.5% (EMPLICITI arm) vs 0.6% (control arm). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values. 
  • Infusion Reactions:
    • Infusion reactions were reported in 3.3% of patients treated with EMPLICITI in the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone (EPd) vs pomalidomide + dexamethasone (Pd)].
    • The only infusion reaction symptom was chest discomfort (2%), which was Grade 1. All the patients who experienced an infusion reaction had them during the first treatment cycle.
    • If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
    • Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen prior to EMPLICITI infusion.
  • Infections:
    • In the ELOQUENT-3 trial (N=115), infections were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3-4 infections were reported in 13% (EPd) and 22% (Pd). Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd). 
    • Monitor patients for development of infections and treat promptly.
  • 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. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These reactions can be fatal. Consider POMALYST interruption or discontinuation for Grade 2-3 skin rash. Permanently discontinue POMALYST for Grade 4 rash, exfoliative or bullous rash, or any other severe cutaneous reactions such as SJS, TEN or DRESS.
  • 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 (SPMs):
    • Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
    • In the EMPLICITI ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and 1.8% (Pd).
    • Monitor patients for the development of SPMs.
  • 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.
  • Interference With Determination of Complete Response: EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
  • Hypersensitivity: Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to POMALYST have been reported. Permanently discontinue POMALYST for angioedema or anaphylaxis.

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 ISATUXIMAB-IRFC

  • Infusion Reactions: Interrupt isatuximab-irfc and manage medically. Permanently discontinue for Grade ≥3 reactions.
  • Neutropenia: Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. Isatuximab-irfc dose delays and the use of colony-stimulating factor may be required to allow improvement of neutrophil count.
  • Second Primary Malignancies (SPM): Monitor patients for the development of SPM, as per IMWG guidelines.
  • Laboratory Test Interference:
    • Interference With Serological Testing (Indirect Antiglobulin Test): Isatuximab-irfc may result in false positive indirect antiglobulin test (indirect Coombs test). Type and screen patients prior to starting treatment. Inform blood banks that a patient has received isatuximab-irfc.
    • Interference With Serum Protein Electrophoresis and Immunofixation Tests: Isatuximab-irfc may interfere with the assays used to monitor M-protein, which may impact the determination of complete response.
  • Embryo-Fetal Toxicity: Can cause fetal harm.

ADVERSE REACTIONS FOR POMALYST AND EMPLICITI

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%), fatigue and asthenia (47%), upper respiratory tract infection (31%), thrombocytopenia (30%), pyrexia (27%), dyspnea (25%), diarrhea (22%), constipation (22%), back pain (20%), cough (20%), pneumonia (19%), bone pain (18%), edema peripheral (17%), peripheral neuropathy (17%), muscle spasms (15%), 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%), thrombocytopenia (22%), and pneumonia (16%).

Serious adverse reactions in the EMPLICITI ELOQUENT-3 trial were 22% (EPd) and 15% (Pd). The most frequent serious adverse reactions in the EPd arm compared to the Pd arm were: pneumonia (13%, 11%) and respiratory tract infection (7%, 3.6%).

The most common adverse reactions in EPd arm (≥20% EPd) and Pd, respectively, were constipation (22%, 11%) and hyperglycemia (20%, 15%).

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 + isatuximab-irfc (Pd-Isa)

The most common adverse reactions (≥20% of patients receiving Pd-Isa or Pd, respectively) were neutropenia (laboratory abnormality, 96%, 92%), infusion-related reactions (38%, 0%), pneumonia (31%, 23%), upper respiratory tract infection (57%, 42%), and diarrhea (26%, 19%). The most common hematology laboratory abnormalities (≥80% of patients) were anemia, neutropenia, lymphopenia, and thrombocytopenia.

Serious adverse reactions in >5% of patients who received Pd-Isa included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%).

DRUG INTERACTIONS FOR POMALYST

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg.

USE IN SPECIFIC POPULATIONS FOR POMALYST AND EMPLICITI

  • Pregnancy: See Boxed WARNINGS for POMALYST: 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, a Bristol Myers Squibb company, at 1-888-423-5436.
  • Pregnancy and EMPLICITI Use: There are no available data on EMPLICITI use in pregnant women to inform a drug-associated risk of major defects and miscarriage.
  • Lactation: There is no information regarding the presence of pomalidomide or elotuzumab in human milk, the effects of POMALYST or EMPLICITI on the breastfed child, or the effects of POMALYST or EMPLICITI 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 or POMALYST in combination with EMPLICITI.
  • 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: For patients with severe renal impairment requiring dialysis, reduce the recommended dosage to 3 mg orally daily. Take dose of POMALYST following hemodialysis on hemodialysis days.
  • Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce POMALYST dosage to 3 mg orally daily and to 2 mg orally daily in patients with severe hepatic impairment.
  • Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces pomalidomide AUC due to CYP1A2 induction.

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

Information about POMALYST + dex + daratumumab (dara), POMALYST + dex + EMPLICITI, and POMALYST + dex + isatuximab (isa) does not appear in the POMALYST full Prescribing Information. Please see the dara, EMPLICITI, and isa full Prescribing Information for a discussion of Important Safety Information at www.darzalex.com (dara), www.empliciti.com (EMPLICITI), and www.sarclisa.com, (isa).