Pomalidomide (Pomalyst)


Pomalyst

Indication: Pomalidomide (Pomalyst) is indicated for patients with multiple myeloma (MM) who have received at least 2 prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of the last therapy.1

Pharmacology: Pomalidomide is an analog of thalidomide, an immunomodulatory agent with antineoplastic activity. Pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of lenalidomide-resistant MM 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 (NK), cell-mediated immunity and inhibited production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, and IL-12.1

Clinical Trials: The trial that led to the approval of pomalidomide was MM-002, a phase II, randomized, open-label study evaluating pomalidomide (4 mg once daily on days 1 through 21 of each 28-day cycle) plus low-dose dexamethasone (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 20 mg per day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients greater than 75 years of age) vs pomalidomide (4 mg once daily on days 1 through 21 of each 28-day cycle) alone in patients with relapsed MM who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib.1

Trial results showed a 29.2% objective response rate in 113 patients treated with pomalidomide plus low-dose dexamethasone vs 7.4% of 109 patients treated with pomalidomide alone. A 7.4-month median duration of response was observed in the combination arm. Median progression-free survival (PFS) was 3.8 months in the combination arm vs 2.5 months in the pomalidomide-alone arm (P=0.007). Overall survival (OS) was 14.4 months with the combination treatment compared with 13.6 months with pomalidomide alone (P=0.85).1

Pomalidomide also has shown activity among MM patients refractory to both lenalidomide and bortezomib.2 A trial conducted by Lacy and colleagues also reported a high degree of activity and response rates with pomalidomide in combination with dexamethasone for MM patients who had relapsed on or were refractory to lenalidomide, thalidomide, or bortezomib.3 Following treatment, 38 of 60 patients (63%) achieved a confirmed response, including a complete response in 3 patients (5%), a very good partial response in 17 patients (28%), and a partial response in 18 patients (30%). Responses were observed in 40% of lenalidomide-refractory patients, 37% of thalidomide-refractory patients, and 60% of bortezomib-refractory patients.

Patients were given pomalidomide 2 mg/day was given orally on days 1 through 28 of a 28-day cycle, while dexamethasone 40 mg/day was given orally on days 1, 8, 15, and 22 of each cycle.3

Pomalidomide plus low-dose dexamethasone significantly improved PFS and OS in patients with relapsed/refractory MM vs high-dose dexamethasone alone, and, therefore, should be considered a new treatment option for patients who have exhausted lenalidomide and bortezomib, according to an analysis of the MM-003 study..4

Warnings/Precautions: Pomalidomide is contraindicated in pregnancy, as it is a known teratogen that causes severe birth defects or embryo fetal death. Females of reproductive potential must avoid pregnancy while taking pomalidomide and at least 4 weeks after completing the therapy. Women must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping pomalidomide. They must obtain 2 negative pregnancy tests prior to initiating therapy. The first test should be performed within 10 to 14 days, a second within 24 hours prior to administering pomalidomide, then weekly during the first month, and monthly thereafter in women with regular menstrual cycles (every 2 weeks  if they have irregular menstrual cycles).1

If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to pomalidomide to the Food and Drug Administration via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436.1 (Important note: the drug is only available through a restricted Risk Evaluation and Mitigation Strategies (REMS)  distribution program called POMALYST REMS.)

 Pomalidomide also presents in semen; therefore males must use a latex/synthetic condom during sexual contact with females while taking pomalidomide and for up to 28 days after stopping the therapy. They should not donate sperm if they are taking pomalidomide. Patients must not donate blood during treatment with pomalidomide and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to the drug. Patients taking pomalidomide may develop venous thromboembolic events; it’s reported as one of the severe adverse reactions. [U.S. Boxed Warning] Venous thromboembolic events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) have occurred during pomalidomide therapy. Consider individualized anticoagulation prophylaxis based on patient risk factors. Neutropenia, anemia, and thrombocytopenia also have been reported. It is important to monitor blood counts weekly for the first 8 weeks and then monthly thereafter.1

Adverse Reactions: The most common adverse effects associated with pomalidomide are fatigue/weakness (55%), peripheral edema, constipation, diarrhea, rash, nausea, suppressed appetite, hypercalcemia, anemia, neutropenia, thrombocytopenia, neuromuscular and skeletal pain, dizziness, fever, renal failure, upper respiratory infection, pneumonia, and dyspnea.1

Drug Interactions: Pomalidomide, primarily metabolized by CYP1A2, and CYP3A, is also a substrate for P-glycoprotein (P-gp). No formal drug interaction studies have been conducted with pomalidomide; however, strong inhibitors of CYP1A2, CYP3A, and P-gp can increase pomalidomide exposures and should be avoided.1

Dosage and Administration: The recommended starting dose of pomalidomide is 4 mg once daily orally on Days 1 through 21 of repeated 28-day cycles until disease progression. Pomalidomide may be given in combination with dexamethasone. Pomalidomide may be taken with water. Inform patients not to break, chew, or open the capsules. Pomalidomide should be taken without food (at least 2 hours before or 2 hours after a meal).1


References

  1. Pomlyst [package insert]. Summit, NJ: Celgene Corp; 2013. http://hemonc.org/w/images/a/a0/Pomalidomide.pdf. Accessed March 17, 2013.
  2. Vij R, Richardson PG, Jagannath S, et al. Pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Outcomes in pts refractory to lenalidomide (LEN) and/or bortezomib (BORT). J Clin Oncol. 2012;30(suppl). Abstract 8016.
  3. Lacy M, Hayman S, Gertz M, et al. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009;27:5008-5014.
  4. Dimopoulos MA, Lacy MQ, Moreau P, et al. Pomalidomide in combination with low-dose dexamethasone demonstrates a significant progression free survival and overall survival advantage, in relapsed/refractory MM: a phase 3, multicenter, randomized, open-label study. Blood (ASH Annual Meeting Abstracts). 2012;120(21):LBA-6.


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