Pomalidomide

POMALYST is a thalidomide analogue indicated for the treatment of adult patients: • in combination with dexamethasone, for patients with multiple myeloma (MM) 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. • with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are HIV-negative. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Pomalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of pomalidomide are mediated through its target cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex. In vitro, in the presence of drug, substrate proteins (including Aiolos and Ikaros) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects. 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 (MM) cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis.

• MM: 4 mg per day taken orally on Days 1 through 21 of repeated 28-day cycles until disease progression. Refer to section 14.1 for dexamethasone dosing. • KS: 5 mg per day taken orally on Days 1 through 21 of repeated 28-day cycles until disease progression or unacceptable toxicity. • Modify the dosage for certain patients with renal impairment or hepatic impairment.

• Pregnancy. • Hypersensitivity Pregnancy POMALYST is contraindicated in females who are pregnant. POMALYST can cause fetal harm when administered to a pregnant female. Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.

Boxed warning: is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe life-threatening birth defects. • For females of reproductive potential: Exclude pregnancy before start of treatment. Prevent pregnancy during treatment by the use of 2 reliable methods of contraception. POMALYST is available only through a restricted program called PS-Pomalidomide REMS. • Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue. • Hematologic Toxicity: Neutropenia was the most frequently reported Grade 3/4 adverse event. Monitor patients for hematologic toxicities, especially neutropenia. • Hepatotoxicity: Hepatic failure including fatalities, monitor liver function tests monthly. • Severe Cutaneous Reactions: Discontinue POMALYST for severe reactions.

The following clinically significant adverse reactions are described in detail in other labeling sections: • Embryo-Fetal Toxicity • Venous and Arterial Thromboembolism • Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone • Hematologic Toxicity • Hepatotoxicity • Severe Cutaneous Reactions • Dizziness and Confusional State • Neuropathy • Risk of Second Primary Malignancies • Tumor Lysis Syndrome • Hypersensitivity • MM: Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.

Strong CYP1A2 Inhibitors: Avoid concomitant use of strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg.

Store at 20°C-25°C (68°F-77°F), excursions permitted to 15°C-30°C (59°F-86°F).