On Location Conference Coverage
Continued from page 29
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Patients received subcutaneous LJPC- 401 at doses of either 1 mg , 5 mg , 10 mg , 20 mg , or 30 mg . If the final patient in each dose group did not experience any drug-related toxicity within three days of injection , the researchers escalated doses .
Treatment-emergent adverse events ( TEAEs ), immunogenicity , and physical and laboratory assessments were used to evaluate safety related to drug administration .
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Most patients ( n = 16 ; 88.9 %) reported TEAEs , with four events reported as moderate and 34 reported as mild in severity . There were no differences in the rates of TEAEs across dose groups . The following AEs were the most frequently reported during and following treatment :
• injection-site reactions ( 66.7 %)
• nausea ( 11.1 %)
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• increased alanine aminotransferase ( 11.1 %)
• decreased appetite ( 11.1 %)
• hypoesthesia ( 11.1 %)
In their pharmacokinetic analysis , the investigators found that the maximum serum concentration at 24 hours after administration increased with each dose level
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increase , with the peak serum drug concentrations occurring approximately two to four hours following all doses . Doses up to LJPC-401 20 mg were associated with a greater reduction in serum iron concentrations , but the reduction at 30 mg was lower than that at 20 mg . Researchers observed a significant dose response across all cohorts ( p = 0.0478 ).
While these findings are preliminary , ongoing studies are exploring the drug ’ s
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POMALYST ® ( pomalidomide ) capsules , for oral use
The following is a Brief Summary ; refer to full Prescribing Information for complete product 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 [ see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), and Use in Specific Populations ( 8.1 , 8.3 )].
POMALYST is only available through a restricted distribution program called POMALYST REMS [ see Warnings and Precautions ( 5.2 )]. 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 [ see Warnings and Precautions ( 5.3 )].
1 INDICATIONS AND USAGE 1.1 Multiple Myeloma POMALYST , in combination with dexamethasone , is indicated 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 .
2 DOSAGE AND ADMINISTRATION 2.1 Multiple Myeloma Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating POMALYST [ see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.3 )].
The recommended starting dose of POMALYST is 4 mg once daily orally on Days 1-21 of repeated 28-day cycles until disease progression . POMALYST should be given in combination with dexamethasone .
POMALYST may be taken with water . Inform patients not to break , chew , or open the capsules . POMALYST may be taken with or without food .
2.2 Dose Adjustments for Toxicities
Table 1 : Dose Modification Instructions for POMALYST for Hematologic Toxicities
Toxicity Dose Modification
Neutropenia
• ANC < 500 per mcL or febrile neutropenia ( fever more than or equal to 38.5 ° C and ANC < 1,000 per mcL )
• ANC return to more than or equal to 500 per mcL
• For each subsequent drop < 500 per mcL
• Return to more than or equal to 500 per mcL
Thrombocytopenia
• Platelets < 25,000 per mcL
• Platelets return to > 50,000 per mcL
• For each subsequent drop < 25,000 per mcL
• Return to more than or equal to 50,000 per mcL
• Interrupt POMALYST treatment , follow CBC weekly
• Resume POMALYST treatment at 3 mg daily
• Interrupt POMALYST treatment
• Resume POMALYST treatment at 1 mg less than the previous dose
• Interrupt POMALYST treatment , follow CBC weekly
• Resume POMALYST treatment at 3 mg daily
• Interrupt POMALYST treatment
• Resume POMALYST treatment at 1 mg less than previous dose
ANC , absolute neutrophil count
To initiate a new cycle of POMALYST , the neutrophil count must be at least 500 per mcL and the platelet count must be at least 50,000 per mcL . If toxicities occur after dose reductions to 1 mg , then discontinue POMALYST .
Permanently discontinue POMALYST for angioedema , skin exfoliation , bullae , or any other severe dermatologic reaction [ see Warnings and Precautions ( 5.7 )].
For other Grade 3 or 4 toxicities , hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician ’ s discretion .
2.3 Dosage Adjustment for Strong CYP1A2 Inhibitors 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 % [ see Drug Interactions ( 7.1 )].
2.4 Dosage Adjustment for Patients with Severe Renal Impairment on Hemodialysis For patients with severe renal impairment requiring dialysis , the recommended starting dose is 3 mg daily ( 25 % dose reduction ). Take POMALYST after completion of dialysis procedure on hemodialysis days [ see Use in Specific Populations ( 8.6 )].
2.5 Dosage Adjustment for Patients with Hepatic Impairment For patients with mild or moderate hepatic impairment ( Child-Pugh classes A or B ), the recommended starting dose is 3 mg daily ( 25 % dose reduction ). For patients with severe hepatic impairment ( Child-Pugh class C ), the recommended dose is 2 mg ( 50 % dose reduction ) [ see Use in Specific Populations ( 8.7 )].
4 CONTRAINDICATIONS Pregnancy POMALYST can cause fetal harm when administered to a pregnant female [ see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )]. POMALYST is contraindicated in females who are pregnant . Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis . If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug , the patient should be apprised of the potential risk to a fetus .
5 WARNINGS AND PRECAUTIONS 5.1 Embryo-Fetal Toxicity POMALYST is a thalidomide analogue and is contraindicated for use during pregnancy . Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death [ see Use in Specific Populations ( 8.1 )]. POMALYST is only available through the POMALYST REMS program [ see Warnings and Precautions ( 5.2 )].
Females of Reproductive Potential Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning POMALYST therapy , during therapy , during dose interruptions and for at least 4 weeks after completing therapy .
Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control , beginning 4 weeks prior to initiating treatment with POMALYST , during therapy , during dose interruptions , and continuing for 4 weeks following discontinuation of POMALYST therapy .
Two negative pregnancy tests must be obtained prior to initiating therapy . The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing POMALYST therapy and then weekly during the first month , then monthly thereafter in females with regular menstrual cycles , or every 2 weeks in females with irregular menstrual cycles [ see Use in Specific Populations ( 8.3 )].
Males Pomalidomide is present in the semen of patients receiving the drug . Therefore , males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST , even if they have undergone a successful vasectomy . Male patients taking POMALYST must not donate sperm [ see Use in Specific Populations ( 8.3 )].
Blood Donation Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST .
5.2 POMALYST REMS Program Because of the embryo-fetal risk [ see Warnings and Precautions ( 5.1 )], POMALYST is available only through a restricted program under a Risk Evaluation and Mitigation Strategy ( REMS ), the “ POMALYST REMS ” program .
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 [ see Use in Specific Populations ( 8.3 )] and males must comply with contraception requirements [ see Use in Specific Populations ( 8.3 )].
• 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 .
5.3 Venous and Arterial Thromboembolism Venous thromboembolic events ( deep venous thrombosis and pulmonary embolism ) and arterial thromboembolic events ( myocardial infarction and stroke ) have been observed in patients treated with POMALYST . In Trial 2 , where anticoagulant therapies were mandated , thromboembolic events occurred in 8.0 % of patients treated with POMALYST and low dose-dexamethasone ( Low-dose Dex ), and 3.3 % of patients treated with high-dose dexamethasone .