2009.08.22 – Pomalidomide Active for Treatment of Anemia of Myelofibrosis

Pomalidomide Active for Treatment of Anemia of Myelofibrosis

Pomalidomide Active for Treatment of Anemia of Myelofibrosis

Researchers involved in an international trial have reported that pomalidomide is active for the treatment of anemia associated with myelofibrosis. The details of this study appeared in an early online publication in the Journal of Clinical Oncology on August 3, 2009.[1]
Myelofibrosis is characterized by fibrosis of the bone marrow that leads to bone marrow dysfunction and often to myeloid metaplasia and acute leukemia. Patients with myelofibrosis have anemia and thrombocytopenia and can have increased or decreased leucocyte levels. Myelofibrosis is also associated with abnormalities of JAK2 and MPL genes. Except for allogeneic stem cell transplantation, treatment is unsatisfactory. Non-transplant treatment modalities have not improved the survival associated with this disease. The usual palliative treatments include erythropoietin, androgens, hydroxyurea, and splenectomy. Single-agent Thalomid® (thalidomide) has been associated with significant palliative effects in patients with myeloid metaplasia, including improvement in blood counts and shrinkage of spleen size. However, single-agent therapy with standard doses of Thalomid of 100 mg per day has been associated with significant side effects. Researchers from the M. D. Anderson Cancer Center and the Mayo Clinic have also reported that Revlimid® (lenalidomide) produces significant responses in patients with myelofibrosis and myeloid metaplasia with less toxicity than observed with Thalomid.
Pomalidomide is an oral analog of thalidomide with significant immunomodulatory effects. It stops the growth of blood vessels, stimulates the immune system, and may directly kill cancer cells. Pomalidomide is also an angiogenesis inhibitor. A Phase I study showed a complete remission rate of 17% in patients with relapsed or refractory myeloma with daily pomalidomide.[2] The main side effects were deep vein thrombosis, which occurred early and late. A Phase II study used an alternate-day regimen of pomalidomide in an attempt to decrease thrombotic side effects.[3] The alternate-day schedule appeared to eliminate thrombotic complications. The complete response rate in patients with relapsed myeloma was 10%, and a greater than 50% reduction in paraprotein was achieved in half the patients.
At ASH 2008 daily pomalidomide and low-dose dexamethasone was evaluated in 37 patients with relapsed or refractory myeloma.[4] The overall response rate was 62%, while 24% had a very good partial response.
The current study was a randomized Phase II clinical trial that compared four treatments in 84 patients with myelofibrosis and anemia:
• Pomalidomide (2 mg/d) plus placebo
• Pomalidomide (2 mg/d) plus prednisone
• Pomalidomide (0.5 mg/d) plus prednisone
• Prednisone plus placebo
Pomalidomide was administered in 12 28-day cycles. Twenty patients in this study had improvement of anemia, and 15 became transfusion independent. Responses to pomalidomide ranged from 23% to 36% compared with 19% for the prednisone arm. Response rates were higher in patients receiving more than three cycles of therapy. Responses to pomalidomide with or without prednisone were durable; they lasted from three months to more than 17 months. Responses were better in patients without leucocytosis. JAK2V617F or cytogenetic abnormalities had no impact on response. These authors concluded that pomalidomide was well tolerated in patients with myclofibrosis and active in treating anemia.

Comments: It appears that pomalidomide can be added to Revlimid as an active derivative of thalidomide with possibly fewer side effects.


[1] Tefferi A, Vestovsek S, Barosi G. et al. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. Journal of Clinical Oncology [early online publication]. August 3, 2009.

[2] Schey SA, Field SP, Bartlett JB, et al. Phase I study of an immunomodulator thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. Journal of Clinical Oncology. 2008;22:3269-3276.

[3] Streetly MJ, Gyertson K, Daniel Y, et al. Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation. British Journal of Haematology. 2008;141:41-51

[4] Lacy MQ, Hayman SR, Gertz MA, et al. Pomalidomide (CC4047) plus low-dose dexamethasone (Pom/dex) is highly effective therapy in relapsed multiple myeloma. Blood. 2008;112:320, abstract number 866.