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 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.

Pomalyst is specifically indicated 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.

Pomalyst is supplied as a capsule for oral administration. The recommended starting dose is 4 mg once daily orally on Days 1-21 of repeated 28-day cycles until disease progression. It should be taken without food (at least 2 hours before or 2 hours after a meal). Pomalyst may be given in combination with dexamethasone.

Clinical Results

FDA Approval
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.

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.

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.

Literature References

Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV, Buadi F Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2010 Nov;24(11):1934-9

Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Kyle RA, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009 Oct 20;27(30):5008-14