Indication POMALYST is indicated for the treatment of multiple myeloma in patientswho have:◦ Received at least two prior therapies, including lenalidomide andbortezomib, and◦ Demonstrated disease progression on or within 60 days of completion ofthe last therapy
Dosage and Administration Recommended Dose◦ 4 mg orally once daily on Days 1-21 of repeated 28-day cycle Administration◦ To be administered until disease progression◦ Must be administered with dexamethasone◦ Must be taken with water◦ Should be taken without food (either 2 hours before or after a meal) Dose Modifications◦ Please see full Prescribing Information for dose modification guidelinesassociated with: Hematologic toxicities: neutropenia or thrombocytopena◦ Grade 3 or 4 toxicities (other than neutropenia or thrombocytopenia) Hold POMALYST When toxicity has resolved to Grade 2 or less, restart at 1 mg less thanprevious dose Discontinue if toxicities occur after dose reduction to 1 mg
Considerations for Special PopulationsPatient Group RecommendationsPregnancy Category X• POMALYST is contraindicated during pregnancy• If used during pregnancy or if patient becomespregnant during treatment, patient should be apprisedof the potential hazard to the fetus• If pregnancy occurs during treatment, discontinuedrugNursing mothers • It is unknown whether or not POMALYST is excreted inhuman milk• Decision to discontinue nursing or discontinue therapyshould be made considering the importance of thedrug to the motherPediatric Safety and effectiveness has not been established inpatients <18 years of age
Considerations for Special Populations (cont.)Patient Group RecommendationsFemales ofReproductivePotential & Males• Females of reproductive potential must avoidpregnancy by abstaining or using two methods ofreliable birth control• Contraception should begin 4 weeks before initiatingPOMALYST, during therapy and 4 weeks afterdiscontinuing therapyGeriatric • No dose adjustment is required based on age• In the study, patients >65 years of age were morelikely to experience pneumoniaRenal Impairment • Safety and efficacy have not been evaluated• Avoid use in patients with serum creatinine >3 mg/dLHepatic Impairment • Safety and efficacy have not been evaluated• Avoid use in patients with serum bilirubin >2 mg/dLand AST/ALT >3x upper limits of normal
Mechanism of Action POMALYST is an immunomodulatory agent with antineoplastic activity◦ Thalidomide analogue As shown in in vitro celullar assays◦ Inhibited proliferation of lenalidomide-resistant multiple myeloma celllines◦ Induced tumor cell apoptosis when combined with dexamethasone inboth lenalidomide-sensitive and lenalidomide-resistant cell lines◦ Enhanced T cell- and natural killer cell-mediated activity◦ Inhibited monocyte production of pro-inflammatory cytokines (eg, TNF-alpha and interluekin-6)
PharmacokineticsParameters ValuesTime to Peak 2-3 hoursVolume of distribution 62L-138L (steady state)Protein binding • 12% to 44%• Not concentration dependentMetabolism • Hepatic• Primarily via CYP1A2, CYP3A4Half-life elimination • 9.5 hours (healthy patients)• 7.5 hours (multiple myeloma patients)Excretion • Feces: 15%• Urine: 73%
Drug Interactions No formal studies have been completed CYP3A, CYP1A2, P-gp inhibitors◦ Co-administration with strong CYP3A, CYP1A2, or P-gp inhibitors couldincrease exposure to POMALYST◦ Combination should be avoided CYP3A, CYP1A2, P-gp inducers◦ Co-administration with strong CYP3A, CYP1A2, or P-gp inducers coulddecrease POMALYST exposure◦ Combination should be avoided Dexamethasone◦ Did not affect POMALYST pharmacokinetics Smoking◦ May reduce effectiveness of POMALYST
Contraindications, Warnings and Precautions Contraindications◦ POMALYST is contraindicated in women who are pregnant◦ If drug is used during pregnancy or patient becomes pregnant, patient shouldbe apprised of the risk to the fetus Embryo-Fetal Toxicity◦ POMALYST is a thalidomide-analogue; thalidomide causes severe birth defectsor embryo-fetal death◦ Pregnancy should be avoided during POMALYST therapy and at least 4 weeksafter completing therapy◦ POMALYST is present in male semen Males must always use latex or synthetic condoms during sexual contactwith females of reproductive potential during and 28 days after therapy Males taking POMALYST should not donate sperm◦ Blood donation Blood should not be donated during treatment and up to 1 month aftercompleting treatment since exposed blood may be transferred to a pregnantfemale
POMALYST REMS™ Program Due to embyro-fetal risk, POMALYST is only available through POMALYSTREMS Requirements include:◦ Prescribers must be certified with the REMS program◦ Patients must sign a Patient-Prescriber agreement and comply withREMS requirements Includes pregnancy testing and contraception requirements◦ Pharmacist must be certified with the REMS program May only dispense POMALYST to patients authorized to receivePOMALYST15
Warnings and Precautions Venous Thromboembolism◦ Consider concomitant anti-coagulation prophylaxis based onpatient’s risk Hematologic Toxicity◦ Neutropenia, anemia, andthrombocytopenia were mostcommonly reported◦ Monitor complete blood countsweekly for first 8 weeks, thenmonthly thereafter◦ Dose may require adjustment orholding Hypersensitivity◦ Risk may be higher in patientswho experienced hypersensitivitywith thalidomide or lenalidomide Dizziness and Confusional State◦ Patients should avoid anymedications or situations thatmay cause dizziness or lead toconfusion without proper medicaladvice Neuropathy◦ Patients may experienceneuropathy or peripheralneuropathy Second Primary Malignancy Risk◦ Cases of acute myelogenousleukemia have been reported inpatients receiving POMALYST16
Trial 1 Information Objective◦ Evaluate the safety and efficacy of POMALYST alone or in combination with lowdose dexamethasone (Low-dose Dex) Study Design◦ Multicenter, randomized, open label, phase 2 study Patient Population and Treatment◦ Patients enrolled had relapsed multiple myeloma, were refractory to their lastmyeloma therapy and received lenalidomide and bortezomib Relapse was defined as achieving at least stable disease for at least onetreatment cycle to at least one prior regimen before disease progressed Refractory was defined as disease progression on or within 60 days of lasttherapy◦ Regimen: POMALYST 4mg, once daily for 21 days (of 28-day cycle), alone orin combination with low dose dexamethasone (Low dose Dex) Low dose Dex schedule: Days 1, 8, 15 and 22 of 28-day cycle Patients ≤75 years of age received 40 mg daily; >70 years of age received20 mg daily
Trial 1: Results Overall response rate did not differ based on prior anti-myeloma therapy19Response POMALYST*(N=108)POMALYST/Low doseDex (N=113)Overall Response Rate,n (%)(95% CI)8 (7.4%)(3.3-14.1)33 (29.2%)(21.0-38.5)Complete Response,n (%)0 (0%) 1 (0.9%)Partial Response,n (%)8 (7.4%) 32 (28.3%)Duration of Response,Median (months),(95% CI)NE 7.4(5.1-9.2)*Results are prior to the addition of dexamethasone.CI=confidence interval; NE=not established (median has not yet been reached).
Supply and Pricing Specifications How suppliedo 1-mg, 2-mg, 3-mg, and 4-mg capsules: 21-count and 100-count bottle Storage and Handing◦ Store at room temperature◦ Capsules should not be opened or crushed◦ If powder comes in contact with skin, wash immediately withsoap and water◦ If powder comes in contact with mucous membranes, flush withwater Drug Pricingo AWP/unit price: $596.88/capsule
References POMALYST® (pomalidomide) [package insert]. CelgeneCorporation. Summit, NJ.http://pomalyst.com/docs/prescribing_information.pdf Truven Health Analytics. Red Book Online® Search. Micromedex.