Kaposi's sarcoma:
Indications for: POMALYST
AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) in adults. Kaposi sarcoma in HIV-negative adults.
Clinical Trials:
Multiple Myeloma
Trial 1 was a phase 2, multicenter, randomized open-label study in patients with relapsed multiple myeloma (MM) who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib. Patients were considered relapsed if they had achieved at least stable disease for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease. Patients were considered refractory if they experienced disease progression on or within 60 days of their last therapy. A total of 221 patients were randomized to receive pomalidomide alone or pomalidomide with Low-dose Dex. In Trial 1, the safety and efficacy of pomalidomide 4 mg, once daily for 21 of 28 days, until disease progression, were evaluated alone and in combination with Low-dose Dex (40 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged 75 years or younger, or 20 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged greater than 75 years). Patients in the pomalidomide alone arm were allowed to add Low-dose Dex upon disease progression.
The trial was designed to measure the number of patients whose cancer completely or partially disappeared after treatment (objective response rate, or ORR). The analysis results showed 7.4% (95% CI, 3.3-14.1) of patients treated with Pomalyst alone achieved ORR. In patients treated with Pomalyst plus low-dose dexamethasone, 29.2% (95% CI, 21-38.5) achieved ORR with a 7.4-month (95% CI, 5.1-9.2) median duration of response.
Trial 2 was a Phase 3 multi-center, randomized, open-label study, where Pomalyst + Low-dose Dex therapy was compared to High-dose Dex in adult patients with relapsed and refractory MM, who had received at least two prior treatment regimens, including lenalidomide and bortezomib, and demonstrated disease progression on or within 60 days of the last therapy. A total of 455 patients were enrolled in the trial: 302 in the Pomalyst + Low-dose Dex arm and 153 in the High-dose Dex arm. Patients in the Pomalyst + Low-dose Dex arm were administered 4 mg Pomalyst orally on Days 1 to 21 of each 28-day cycle. Dexamethasone (40 mg) was administered once per day on Days 1, 8, 15 and 22 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. For the High-dose Dex arm, dexamethasone (40 mg) was administered once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. Treatment continued until patients had disease progression.
The primary endpoints assessed were progression free survival (PFS), overall response rate (ORR), and overall survival (OS), which were based on the evaluation by the Independent Review Adjudication Committee (IRAC).
Results showed that PFS was significantly longer with Pomalyst + Low-dose Dex versus High-dose Dex: HR 0.45 (95% CI, 0.35-0.59; P <0.001). OS was also significantly longer with Pomalyst + Low-dose Dex compared to High-dose Dex: HR 0.70 (95% CI, 0.54-0.92; P =0.009). In addition, the ORR was also higher with Pomalyst + Low-dose Dex compared to High-dose Dex (23.5% vs 3.9%), respectively.
Kaposi Sarcoma
The clinical trial 12-C-0047 (NCT01495598), was an open label, single center, single arm clinical study that evaluated the safety and efficacy of Pomalyst in patients with Kaposi sarcoma (KS). A total of 28 patients (18 HIV-positive, 10 HIV-negative) received Pomalyst 5 mg orally once daily on Days 1 through 21 of each 28-day cycle until disease progression or unacceptable toxicity. All HIV-positive patients continued highly active antiretroviral therapy (HAART). Patients received thromboprophylaxis with aspirin 81 mg once daily throughout therapy. Seventy five percent of patients had advanced disease (T1) at the time of enrollment, 11% had ≥ 50 lesions, and 75% had received prior chemotherapy. The major efficacy outcome measure was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR), and partial response (PR). Response was assessed by the investigator according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for KS. The median time to first response was 1.8 months (0.9-7.6).
Results showed an ORR of 71% (95% CI, 51-87) among all patients, with a median duration of response of 12.1 months (95% CI, 7.6-16.8). Among HIV-positive patients, the ORR was 67% (95% CI, 41-87), with a median duration of response of 12.5 months (95% CI, 6.5-24.9). An ORR of 80% (95% CI, 44-98) was observed among HIV-negative patients, with a median duration of response of 10.5 months (95% CI, 3.9-24.2).
Adult Dosage:
Confirm negative pregnancy status before initiation. Swallow whole; may be taken with water (with or without food). 5mg once daily on Days 1–21 of each 28-day cycle until disease progression or unacceptable toxicity; continue HAART in AIDS patients. Concomitant strong CYP1A2 inhibitors (if unavoidable): reduce Pomalyst dose to 2mg. Severe renal impairment requiring dialysis: 4mg daily; give dose after dialysis session on hemodialysis days. Hepatic impairment: 3mg daily. Dose modifications for adverse reactions, other Grade 3/4 toxicities: see full labeling.
Children Dosage:
Not established.
POMALYST Contraindications:
Pregnancy.
Boxed Warning:
Embryo-fetal toxicity. Venous and arterial thromboembolism.
POMALYST Warnings/Precautions:
Embryo-fetal toxicity: females of reproductive potential must avoid pregnancy, commit either to abstain from heterosexual sex or to use two methods of reliable contraception, at least 4 weeks prior to initiating, during therapy, dose interruptions and for at least 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24hrs prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 4 weeks after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation. Venous and arterial thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); withhold, reduce dose, or permanently discontinue based on severity of reaction. Obtain CBCs weekly for first 8 weeks (for MM) or every 2 weeks for first 12 weeks (for KS), and monthly thereafter. Hepatic or severe renal impairment on hemodialysis: adjust doses (see Adults). Monitor LFTs monthly; discontinue and evaluate if elevated liver enzymes occur; consider using lower dose when restarting. Risk of second primary malignancies. High tumor burden (monitor). Permanently discontinue if angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or other severe cutaneous reactions occur (eg, SJS, TEN, DRESS). Nursing mothers: not recommended.
POMALYST Classification:
Immunomodulator.
POMALYST Interactions:
Increased mortality when PD-1 or PD-L1 blocking antibody (eg, pembrolizumab) is added to thalidomide analogue plus dexamethasone regimen in multiple myeloma: not recommended. Potentiated by strong CYP1A2 inhibitors (eg, ciprofloxacin, fluvoxamine); avoid (see Adults). Smoking may reduce efficacy.
Adverse Reactions:
Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infections, back pain, pyrexia, rash, elevated creatinine, glucose, or ALT, decreased hemoglobin, platelets, phosphate, albumin, or calcium; thrombocytopenia, hepatotoxicity, dizziness, confusion, neuropathy, pneumonia, tumor lysis syndrome, severe cutaneous or hypersensitivity reactions.
Note:
Available only through Pomalyst REMS program. More information about the Pomalyst REMS program is available at www.celgeneriskmanagement.com or call (888) 423-5436.
Drug Elimination:
Pomalidomide is eliminated with a median plasma half-life of 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS.
Following a single oral administration of [14C]-pomalidomide to healthy subjects, ~73% and 15% of the radioactive dose was eliminated in urine and feces, respectively, with ~2% and 8% of the radiolabeled dose eliminated unchanged as pomalidomide in urine and feces.
REMS:
Generic Drug Availability:
YES
How Supplied:
Caps—21, 100
Leukemias, lymphomas, and other hematologic cancers:
Indications for: POMALYST
In combination with dexamethasone for multiple myeloma (MM), in patients who have received at least two prior therapies (including lenalidomide and a proteasome inhibitor), and have shown disease progression on or within 60 days of completion of the last therapy.
Clinical Trials:
Multiple Myeloma
Trial 1 was a phase 2, multicenter, randomized open-label study in patients with relapsed multiple myeloma (MM) who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib. Patients were considered relapsed if they had achieved at least stable disease for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease. Patients were considered refractory if they experienced disease progression on or within 60 days of their last therapy. A total of 221 patients were randomized to receive pomalidomide alone or pomalidomide with Low-dose Dex. In Trial 1, the safety and efficacy of pomalidomide 4 mg, once daily for 21 of 28 days, until disease progression, were evaluated alone and in combination with Low-dose Dex (40 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged 75 years or younger, or 20 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged greater than 75 years). Patients in the pomalidomide alone arm were allowed to add Low-dose Dex upon disease progression.
The trial was designed to measure the number of patients whose cancer completely or partially disappeared after treatment (objective response rate, or ORR). The analysis results showed 7.4% (95% CI, 3.3-14.1) of patients treated with Pomalyst alone achieved ORR. In patients treated with Pomalyst plus low-dose dexamethasone, 29.2% (95% CI, 21-38.5) achieved ORR with a 7.4-month (95% CI, 5.1-9.2) median duration of response.
Trial 2 was a Phase 3 multi-center, randomized, open-label study, where Pomalyst + Low-dose Dex therapy was compared to High-dose Dex in adult patients with relapsed and refractory MM, who had received at least two prior treatment regimens, including lenalidomide and bortezomib, and demonstrated disease progression on or within 60 days of the last therapy. A total of 455 patients were enrolled in the trial: 302 in the Pomalyst + Low-dose Dex arm and 153 in the High-dose Dex arm. Patients in the Pomalyst + Low-dose Dex arm were administered 4 mg Pomalyst orally on Days 1 to 21 of each 28-day cycle. Dexamethasone (40 mg) was administered once per day on Days 1, 8, 15 and 22 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. For the High-dose Dex arm, dexamethasone (40 mg) was administered once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle. Patients >75 years of age started treatment with 20 mg dexamethasone using the same schedule. Treatment continued until patients had disease progression.
The primary endpoints assessed were progression free survival (PFS), overall response rate (ORR), and overall survival (OS), which were based on the evaluation by the Independent Review Adjudication Committee (IRAC).
Results showed that PFS was significantly longer with Pomalyst + Low-dose Dex versus High-dose Dex: HR 0.45 (95% CI, 0.35-0.59; P <0.001). OS was also significantly longer with Pomalyst + Low-dose Dex compared to High-dose Dex: HR 0.70 (95% CI, 0.54-0.92; P =0.009). In addition, the ORR was also higher with Pomalyst + Low-dose Dex compared to High-dose Dex (23.5% vs 3.9%), respectively.
Kaposi Sarcoma
The clinical trial 12-C-0047 (NCT01495598), was an open label, single center, single arm clinical study that evaluated the safety and efficacy of Pomalyst in patients with Kaposi sarcoma (KS). A total of 28 patients (18 HIV-positive, 10 HIV-negative) received Pomalyst 5 mg orally once daily on Days 1 through 21 of each 28-day cycle until disease progression or unacceptable toxicity. All HIV-positive patients continued highly active antiretroviral therapy (HAART). Patients received thromboprophylaxis with aspirin 81 mg once daily throughout therapy. Seventy five percent of patients had advanced disease (T1) at the time of enrollment, 11% had ≥ 50 lesions, and 75% had received prior chemotherapy. The major efficacy outcome measure was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR), and partial response (PR). Response was assessed by the investigator according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for KS. The median time to first response was 1.8 months (0.9-7.6).
Results showed an ORR of 71% (95% CI, 51-87) among all patients, with a median duration of response of 12.1 months (95% CI, 7.6-16.8). Among HIV-positive patients, the ORR was 67% (95% CI, 41-87), with a median duration of response of 12.5 months (95% CI, 6.5-24.9). An ORR of 80% (95% CI, 44-98) was observed among HIV-negative patients, with a median duration of response of 10.5 months (95% CI, 3.9-24.2).
Adult Dosage:
Confirm negative pregnancy status before initiation. Swallow whole; may be taken with water (with or without food). 4mg once daily on Days 1–21 of each 28-day cycle until disease progression; give with dexamethasone. Concomitant strong CYP1A2 inhibitors (if unavoidable): reduce Pomalyst dose to 2mg. Severe renal impairment requiring dialysis: 3mg daily; give dose after dialysis session on hemodialysis days. Hepatic impairment (mild or moderate): 3mg daily; (severe): 2mg daily. Dose modifications for adverse reactions, other Grade 3/4 toxicities: see full labeling.
Children Dosage:
Not established.
POMALYST Contraindications:
Pregnancy.
Boxed Warning:
Embryo-fetal toxicity. Venous and arterial thromboembolism.
POMALYST Warnings/Precautions:
Embryo-fetal toxicity: females of reproductive potential must avoid pregnancy, commit either to abstain from heterosexual sex or to use two methods of reliable contraception, at least 4 weeks prior to initiating, during therapy, dose interruptions and for at least 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24hrs prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 4 weeks after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation. Venous and arterial thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); withhold, reduce dose, or permanently discontinue based on severity of reaction. Obtain CBCs weekly for first 8 weeks (for MM) or every 2 weeks for first 12 weeks (for KS), and monthly thereafter. Hepatic or severe renal impairment on hemodialysis: adjust doses (see Adults). Monitor LFTs monthly; discontinue and evaluate if elevated liver enzymes occur; consider using lower dose when restarting. Risk of second primary malignancies. High tumor burden (monitor). Permanently discontinue if angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or other severe cutaneous reactions occur (eg, SJS, TEN, DRESS). Nursing mothers: not recommended.
POMALYST Classification:
Immunomodulator.
POMALYST Interactions:
Increased mortality when PD-1 or PD-L1 blocking antibody (eg, pembrolizumab) is added to thalidomide analogue plus dexamethasone regimen in multiple myeloma: not recommended. Potentiated by strong CYP1A2 inhibitors (eg, ciprofloxacin, fluvoxamine); avoid (see Adults). Smoking may reduce efficacy.
Adverse Reactions:
Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infections, back pain, pyrexia, rash, elevated creatinine, glucose, or ALT, decreased hemoglobin, platelets, phosphate, albumin, or calcium; thrombocytopenia, hepatotoxicity, dizziness, confusion, neuropathy, pneumonia, tumor lysis syndrome, severe cutaneous or hypersensitivity reactions.
Note:
Available only through Pomalyst REMS program. More information about the Pomalyst REMS program is available at www.celgeneriskmanagement.com or call (888) 423-5436.
Drug Elimination:
Pomalidomide is eliminated with a median plasma half-life of 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS.
Following a single oral administration of [14C]-pomalidomide to healthy subjects, ~73% and 15% of the radioactive dose was eliminated in urine and feces, respectively, with ~2% and 8% of the radiolabeled dose eliminated unchanged as pomalidomide in urine and feces.
REMS:
Generic Drug Availability:
YES
How Supplied:
Caps—21, 100
