MMPB17DDBH6969-POMALYST DPD Email

For detailed information on POMALYST in combination with dexamethasone, click here

POMALYST + dexamethasone + daratumumab is indicated for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor²

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

In an open-label trial (N=103)²:

59% of patients achieved a response with POMALYST + dex + daratumumab with 42% reaching a VGPR or better

ORR: 59.2% [95% CI 49.1, 68.8]

ORR= sCR (7.8%) + CR (5.8%) + VGPR (28.2%) + PR (17.5%)

Efficacy results were based on ORR as determined by Independent Review Committee using IMWG criteria.

CR, complete response; dex, dexamethasone; IMWG, International Myeloma Working Group; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.

Median time to response was 1 month (range: 0.9 to 2.8 months)

Median duration of response was 13.6 months (range: 0.9+ to 14.6+ months)

Open-label trial (without a comparator arm) where POMALYST + dex + daratumumab was studied in 103 patients with multiple myeloma who had received a prior proteasome inhibitor and REVLIMID^® (lenalidomide)

•	Median age was 64 years (range, 35-86)

All patients in the trial received prior REVLIMID

•	POMALYST was given orally at 4 mg once daily on Days 1-21 of repeated 28-day cycles

•	Daratumumab 16 mg/kg was administered as an intravenous infusion weekly (Weeks 1-8), every 2 weeks (Weeks 9-24), and every 4 weeks from Week 25 until disease progression

•	Low-dose dex was given orally or intravenously 40 mg/week*

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On daratumumab infusion days, 20 mg of the dex dose was given as a pre-infusion medication and the remainder given the day after the infusion

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For patients on a reduced dex dose, the entire 20 mg dose was given as a daratumumab pre-infusion medication

*	Reduced dose of 20 mg/week for patients >75 years or body mass index (BMI) <18.5.

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.

DARATUMUMAB: WARNINGS AND PRECAUTIONS

•	Infusion reactions: Interrupt daratumumab infusion for infusion reactions of any severity. Permanently discontinue the infusion in case of life-threatening infusion reactions.

•	Interference with cross-matching and red blood cell antibody screening: 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.

13% of patients discontinued treatment due to adverse reaction(s)

The most frequent adverse reactions of any grade (≥20%) included (N=103):

•	Neutropenia (95%)
•	Lymphopenia (94%)
•	Thrombocytopenia (75%)
•	Anemia (57%)
•	Infusion reactions (50%)
•	Fatigue (50%)
•	Upper respiratory tract infection (50%)
•	Cough (43%)
•	Diarrhea (38%)

Median treatment duration was 6 months (range 0.03 to 16.9 months).

The overall incidence of serious adverse reactions was 49%. Serious adverse reactions reported in ≥5% patients included pneumonia (7%).

Grade 3/4 hematology
laboratory abnormalities included (N=103):

•	Lymphopenia (Grade 3, 45%; Grade 4, 26%)
•	Neutropenia (Grade 3, 36%; Grade 4, 46%)
•	Anemia (Grade 3, 30%; Grade 4, 0%)
•	Thrombocytopenia (Grade 3, 10%; Grade 4, 10%)

Please see the daratumumab full PI for a discussion
of Important Safety Information at www.darzalex.com.

POMALYST Important Safety Information (continued)¹

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

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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.

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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

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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.

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Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-8‌88-423-54‌36.

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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.

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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.

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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.

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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.

•	Hypersensitivity Reactions: Angioedema and severe dermatologic reactions have been reported. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reactions, and do not resume therapy.

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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

Nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). The most common adverse reactions (≥15%) 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%) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

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

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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.

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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.

References:

1.	POMALYST [package insert]. Summit, NJ: Celgene Corp; 2018.
2.	Daratumumab [package insert]. Horsham, PA: Janssen Biotech, Inc; 2019.

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

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