Pomalyst (pomalidomide) - 2 indications

Scroll down for additional information on each indication:

for the treatment of relapsed and refractory multiple myeloma; approved February 2013

for AIDS-Related and HIV-Negative Kaposi Sarcoma; approved May 2020

General Information

Pomalyst (pomalidomide) is an immunomodulatory antineoplastic agent. It inhibits proliferation and induces apoptosis of hematopoietic tumor cells, enhances T cell- and natural killer cell-mediated immunity and inhibits production of pro-inflammatory cytokines by monocytes.

Pomalyst is specifically indicated for the following:

• patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy.
• patients with AIDS-related Kaposi sarcoma whose disease has become resistant to highly active antiretroviral therapy (HAART), or in patients with Kaposi sarcoma who are HIV-negative.

Pomalyst is supplied as a capsule for oral administration. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Pomalidomide, an analogue of thalidomide, is an immunomodulatory agent with antineoplastic activity. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of lenalidomide-resistant multiple myeloma cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis. Pomalidomide enhanced T cell- and natural killer cell-mediated immunity and inhibited production of pro-inflammatory cytokines by monocytes.

Side Effects

Adverse events associated with the use of Pomalyst for MM may include, but are not limited to, the following:

• fatigue and asthenia
• neutropenia
• anemia
• constipation
• nausea
• diarrhea
• dyspnea
• upper-respiratory tract infections
• back pain
• pyrexia

Adverse effects associated with the use of Pomalyst for Kaposi sarcoma may include, but are not limited to, the following:

• decreased absolute neutrophil count or white blood cells
• elevated creatinine or glucose
• rash
• constipation
• fatigue
• decreased hemoglobin, platelets, phosphate, albumin, or calcium
• increased ALT
• nausea
• diarrhea

The Pomalyst drug label comes with the following Black Box Warning: 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.

Indication 1 - for the treatment of relapsed and refractory multiple myeloma

approved February 2013

Dosing/Administration

The recommended dosage of Pomalyst is 4 mg once daily orally with or without food on Days 1 through 21 of each 28-day cycle until disease progression. Give Pomalyst in combination with dexamethasone.

Clinical Trial Results

The FDA approval of Pomalyst was based on a multicenter, randomized open label study in 221 subjects with relapsed multiple myeloma who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib. The subjects received Pomalyst 4 mg, once daily for 21 of 28 days, until disease progression, alone and in combination with Low dose Dex (40 mg per day given only on Days 1, 8, 15 and 22 of each 28-day cycle for patients 75 years or younger, or 20mg per day given only on Days 1, 8, 15 and 22 of each 28-day cycle for patients greater than 75 years of age). Subjects in the Pomalyst alone arm were allowed to add Low dose Dex upon disease progression. The overall response rate was 29.2% vs. 7.4%, the complete response was 0.9% vs. 0.0% and the partial response was 28.3% vs. 7.4% in the Pomalyst + low dose dex arm vs. the Pomalyst alone arm, respectively.

Indication 2 - for AIDS-Related and HIV-Negative Kaposi Sarcoma

approved May 2020

Dosing/Administration

The recommended dosage of Pomalyst is 5 mg once daily taken orally with or without food on Days 1 through 21 of each 28-day cycle until disease progression or unacceptable toxicity. Continue HAART as HIV treatment in patients with AIDS-related Kaposi sarcoma.

Clinical Trial Results

The FDA granted accelerated approval to Pomalyst for patients with AIDS-related Kaposi sarcoma whose disease has become resistant to highly active antiretroviral therapy (HAART), or in patients with Kaposi sarcoma who are HIV-negative was based on overall response rates observed in a Phase 1/2 open label, single-arm clinical trial (12-C-0047). Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial. A total of 28 patients (18 HIV-positive, 10 HIV-negative) received 5 mg of Pomalyst, once daily for 21 of 28-day cycles, until disease progression or unacceptable toxicity. All HIV-positive patients continued concomitant highly active antiretroviral therapy (HAART). The trial excluded patients with symptomatic pulmonary or visceral Kaposi sarcoma, history of venous or arterial thromboembolism, or procoagulant disorders. The primary endpoint of the study was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR) and partial response (PR), as assessed by investigators according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for Kaposi sarcoma. For all patients, the ORR was 71%, with 14% (4/28) of patients achieving CR and 57% (16/28) of patients achieving a PR, respectively. The median duration of response for all patients was 12.1 months. Additionally, half (50%) of patients who responded maintained a response at more than 12 months.