Multiple Myeloma: Pomalidomide, in combination with dexamethasone, is indicated for adult patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor, and who have shown disease progression during or within 60 days after completion of the last therapy.

Kaposi Sarcoma: Pomalidomide is indicated for the treatment of:

• Adult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART)
• Kaposi sarcoma (KS) in HIV-negative adult patients

Pomalidomide is an analogue of thalidomide with immunomodulatory, anti-angiogenic, and antineoplastic properties. Its cellular effects are mediated through binding to cereblon, a component of the cullin ring E3 ubiquitin ligase complex. In the presence of the drug, substrate proteins such as Aiolos and Ikaros are targeted for ubiquitination and degradation, leading to cytotoxic and immunomodulatory effects. In vitro studies show that pomalidomide inhibits proliferation and induces apoptosis in hematologic tumor cells. It is active against lenalidomide-resistant multiple myeloma cell lines and shows synergistic effects with dexamethasone in inducing tumor cell apoptosis in both sensitive and resistant lines. It enhances T-cell and natural killer (NK) cell–mediated immunity and reduces pro-inflammatory cytokines such as TNF-α and IL-6. It also demonstrates anti-angiogenic activity in animal and in vitro models.

Pharmacodynamics Exposure–response analyses indicate no clear relationship between systemic exposure of pomalidomide and efficacy or safety at the 4 mg dose level.

Pharmacokinetics In multiple myeloma patients receiving 4 mg daily (alone or with dexamethasone), steady-state exposure showed AUC of 860 ng·h/mL (CV 37%) and Cmax of 75 ng/mL (CV 32%). In Kaposi sarcoma patients receiving 5 mg daily, AUC was 462.3 ng·h/mL (82%) and Cmax was 53.1 ng/mL (50%).

Absorption After oral administration, peak plasma concentration (Cmax) occurs within 2–3 hours post-dose in MM and KS patients.

Distribution Pomalidomide has an apparent volume of distribution of 62–138 L at steady state. It is distributed in semen at about 67% of plasma concentration. Plasma protein binding ranges from 12% to 44% and is concentration independent. It is a substrate of P-glycoprotein (P-gp).

Metabolism It is primarily metabolized in the liver via CYP1A2 and CYP3A4, with minor contribution from CYP2C19 and CYP2D6.

Elimination Total body clearance is 7–10 L/h. The mean plasma half-life is about 9.5 hours in healthy subjects and 7.5 hours in MM or KS patients.

Excretion After oral administration of radiolabeled drug, about 73% is excreted in urine and 15% in feces. Around 2% (urine) and 8% (feces) is excreted unchanged.

Pregnancy Testing Prior to Administration: Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating Pomalidomide.

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

Recommended Dosage for Kaposi Sarcoma: The recommended dosage of Pomalidomide 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 (KS).

Dosage Modifications for Hematologic Adverse Reactions Multiple Myeloma: Dosage Modifications for Hematologic Adverse Reactions: Initiate a new cycle of Pomalidomide in patients with multiple myeloma (MM) when the neutrophil count is at least 500 per mcL and the platelet count is at least 50,000 per mcL.

Kaposi Sarcoma: Dosage Modifications for Hematologic Adverse Reactions Initiate a new cycle of Pomalidomide in patients with KS when the neutrophil count is at least 1000 per mcL and the platelet count is at least 75,000 per mcL.

Dosage Modifications for Non-Hematologic Adverse Reactions: Permanently discontinue Pomalidomide for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction. 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.

Dosage Modifications for Strong CYP1A2 Inhibitors: Avoid concomitant use of Pomalidomide with strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce Pomalidomide dose to 2 mg.

Pediatric Use: The safety and effectiveness of POMALYST have not been established in pediatric patients.

Strong CYP1A2 Inhibitors: Concomitant use with strong CYP1A2 inhibitors should be avoided. If unavoidable, the dose of Pomalidomide should be reduced to 2 mg.

Multiple Myeloma: The most common adverse reactions (>30%) include fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infection, back pain, and pyrexia.

Kaposi Sarcoma: Common adverse reactions (>30%) include decreased absolute neutrophil count or white blood cells, increased creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea.

Pregnancy: Pomalidomide is contraindicated in pregnancy. It can cause fetal harm and is teratogenic in animals. If pregnancy occurs during treatment, the patient should be informed about the risk to the fetus.

Lactation: There is no information on excretion in human milk or effects on the breastfed infant. However, because many drugs pass into breast milk, breastfeeding should be avoided during treatment.

• Increased Mortality: Increased mortality observed in multiple myeloma patients when pembrolizumab was used with dexamethasone and a thalidomide analogue.
• Hematologic Toxicity: Neutropenia is the most common Grade 3/4 toxicity; monitor blood counts regularly.
• Hepatotoxicity: Liver failure including fatal cases reported; monitor liver function tests monthly.
• Severe Cutaneous Reactions: Discontinue drug if severe skin reactions occur.
• Tumor Lysis Syndrome: Monitor high-risk patients carefully and take preventive measures.
• Hypersensitivity: Monitor for allergic reactions; discontinue in case of angioedema or anaphylaxis.

Store below 30°C, protected from light and moisture. Keep out of reach of children.