Revlimid® Shows Promise in Treatment of Myelofibrosis with Myeloid Metaplasia

According to the results of two phase II clinical trials published in the journal Blood, treatment with Revlimid® (lenalidomide) produces promising results in patients with myelofibrosis with myeloid metaplasia (MMM).

MMM is characterized by bone marrow dysfunction and enlargement of the spleen. It can ultimately lead to acute leukemia. Treatment may involve use of medications to relieve symptoms, or more aggressive treatment such as stem cell transplantation.

Use of thalidomide has been shown to improve blood counts and to result in shrinkage of the spleen in patients with MMM, but this treatment carries significant risk of side effects. Revlimid is a derivative of thalidomide that appears to produce fewer side effects.

To explore the safety and effectiveness of Revlimid in the treatment of MMM, researchers at the MD Anderson Cancer Center and the Mayo Clinical conducted two phase II clinical trials. The trials enrolled a total of 68 patients.

Patients were treated with Revlimid for three to four months, with a plan to continue treatment if the patients showed a response to treatment.

22% of patients experienced an improvement in anemia. In eight patients, improvements in anemia were deemed “impressive.” These patients started out with very low hemoglobin levels or transfusion dependence, and experienced a normalization of hemoglobin levels after treatment.
33% of patients experienced a reduction in the size of their spleen.
Serous adverse effects of treatment included neutropenia (low white blood cell levels) and thrombocytopenia (low platelet levels). Thirty-one percent of patients experienced grade 3 or grade 4 neutropenia, and 19% of patients experienced grade 3 or grade 4 thrombocytopenia.
The researchers conclude that Revlimid appears to provide important benefits to a subset of patients with MMM. In these patients, Revlimid improved blood and bone marrow abnormalities.

Aranesp® Effectively Treats Anemia in Patients with Low-risk Myelodysplastic Syndrome

According to results presented at the 2006 annual meeting of the American Society of Clinical Oncology (ASCO), Aranesp® (darbepoetin alfa) administered every three weeks increases red blood cell counts in patients with low-risk myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a group of diseases marked by abnormal production of blood cells by the bone marrow. Healthy bone marrow produces immature blood cells—called blasts—that then develop into red blood cells, white blood cells, and platelets. MDS disrupts this normal process so that the bone marrow is overactive, producing many immature cells. These blasts, however, do not fully develop into mature blood cells. As a result, patients with MDS have fewer mature blood cells, and those they do have may be abnormal and not function properly.

Any or all blood cell types may be affected by MDS, which is different from leukemia in which only white blood cells are overproduced. The direct effects of MDS may include:

Anemia and fatigue if red blood cells counts are low.
Increased risk of infection if white blood cell counts are low.
Compromised ability to control bleeding if platelet counts are low.
Anemia can be treated with a red blood cell transfusion or by increasing red blood cell production with a naturally produced protein called erythropoietin. Erythropoietin stimulates the bone marrow to produce more red blood cells. When administered to some patients, it reduces the severity of anemia and can prevent red blood cell transfusions.

Forms of erythropoietin that are currently available include epoetin alfa (Epogen® or Procrit®) and darbepoetin alfa (Aranesp®). Aranesp is a longer acting form that can be administered less frequently. Aranesp has not yet been approved by the FDA for the treatment of anemia associated with MDS.

To evaluate the use of Aranesp to treat anemia in patients with low- or intermediate risk MDS, researchers are conducting an ongoing 52-week phase II trial involving more than 200 patients. Aranesp (500 mcg) is administered every three weeks. Previous preliminary results from this study indicated that low-risk MDS patients can experience a significant increase in red blood cell count after 13 weeks of Aranesp.

The results presented at ASCO 2006 focused on 27/28 weeks of follow-up.

Among patients who had not previously received medication to increase red blood cell count, 74% of patients achieved the target hemoglobin level of 11 g/dL. None of the patients required a transfusion during the 27/28 week observation period.
Among patients who had previously received medication to increase red blood cell count, 49% of patients achieved the target hemoglobin level of 11 g/dL. Five percent of patients received at least one transfusion during the 27/28 week observation period.
Three complications related to blood clots have occurred thus far.
The researchers conclude that these preliminary results suggest that Aranesp every three weeks is well tolerated and increases red blood cell count in anemic patients with low-risk MDS.

Reference: Paquette R, Gabrilove J, Lyons R et al. Darbepoetin Alfa for Treating Anemia in Low-risk Myelodysplastic Syndrome Patients: Interim Results after 27/28 Weeks. Presented at the 2006 ASCO Annual Meeting. Abstract 6564.

Further Evidence that Vidaza® Reduces Need for Transfusions in Myelodysplastic Syndromes

According to results recently presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO), further evaluation of data demonstrates that the agent Vidaza® (azacitadine) reduces the need for red blood cell and platelet transfusions in a significant portion of patients with myelodysplastic syndromes (MDS).

Myelodysplastic syndromes are a group of blood (hematologic) disorders that are diagnosed in 10,000 to 20,000 individuals annually in the U.S. MDS occurs when immature blood cells do not mature properly and are never able to perform their intended function. They instead crowd out normal blood cells in the bone marrow, often inhibiting other cells from performing their intended functions.

MDS can also develop into an aggressive form of leukemia, acute myelogenous leukemia (AML). Preventing or delaying the development of MDS into AML is an important consideration since long-term survival for AML is not favorable.

The different classifications of MDS range from low-risk to high-risk. Low-risk patients often have less aggressive disease that may be managed with blood transfusions (referred to as transfusion-dependent), which require the infusion of a donor’s red blood cells (cells that deliver oxygen throughout the body) or infusion of a donor’s platelets (cells that help the blood to clot appropriately). High-risk patients may need more aggressive management of their disease.

Since blood transfusions are time consuming, require medical resources, increase medical costs, and are associated with the potential of infection, pain, and other reactions, reducing or preventing the need for transfusions in patients with MDS is a major consideration.

Vidaza is the first ever agent to be approved for the treatment of MDS. Vidaza has previously demonstrated a reduction in the need for transfusions among patients with MDS. However, researchers wanted to further evaluate the effectiveness of Vidaza by studying data from three large clinical trials in which patients with MDS were treated with Vidaza.

The data included a total of 268 patients who were involved in Cancer and Leukemia Group B (CALGB) studies, all of whom were transfusion dependent prior to treatment with Vidaza. “Transfusion independent” in this analysis referred to patients who did not require a transfusion for at least 56 days.

Among patients who were treated with the recommended subcutaneous administration of Vidaza, between 36% and 53% became red blood cell transfusion independent.
Among patients treated with subcutaneous administration of Vidaza, 45%-69% became platelet transfusion independent.
The median duration of transfusion independence over all three studies was approximately 5–8.4 months for red blood cell transfusions and approximately 4–9.5 months for platelet transfusions.
The researchers concluded that further data evaluation has added evidence supporting the use of Vidaza among patients with transfusion-dependent MDS. Treatment with Vidaza allows a significant portion of patients to not require red blood cell or platelet transfusions. Patients with transfusion-dependent MDS may wish to speak with their physician regarding their individual risks and benefits of treatment with Vidaza.

Reference: Silverman L, Peterson, Holland J, et al. Transfusion Independencein Patients with Myelodysplastic Syndromes Treated with Azacitidine. Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. June 2006. Abstract #6576.

Aranesp® Effective for Treating Anemia Associated with “Low-Risk” MDS

According to an article published in the British Journal of Haematology, Aranesp® (darbepoetin alfa) is effective in treating anemia in patients with lower-risk myelodysplastic syndrome (MDS).

Myelodysplastic syndromes are a group of diseases involving the bone marrow. MDS results in inadequate production of red blood cells, white blood cells, and platelets. Therefore, initial treatment is often aimed at restoring levels of these cells to normal. This group of diseases ultimately leads to bone marrow failure or acute leukemia. However, some MDS patients achieve long-term survival with minimal intervention.

MDS tends to occur in elderly people who may have other significant medical problems that prevent aggressive treatment. Current treatments for MDS generally fall into the category of supportive care, particularly with agents that restore red or white blood cell levels. Patients with more advanced disease may also be treated with chemotherapy drugs.

Anemia is a common symptom among patients with MDS. It is characterized by low levels of circulating red blood cells, which are responsible for delivering oxygen to tissues throughout the body.

Common symptoms of anemia are severe fatigue, shortness of breath, diminished activity levels, and a reduced overall feeling of well-being.

Severe anemia often requires treatment with blood transfusions, which have associated risks of infection, rejection, and increased medical costs. Furthermore, severe anemia may cause a delay in cancer treatment, resulting in less favorable chances of a cure or optimal long-term survival.

Use of medications to treat anemia has been shown to have several benefits in cancer patients, including increased quality of life and decreased need for blood transfusions. The effect on survival, however, has been uncertain.

Aranesp treats chemotherapy-induced anemia by stimulating cells in the bone marrow to produce functioning red blood cells, ultimately providing sustained normal levels of red blood cells in the body. It is also being evaluated for the treatment of anemia that is directly caused by the cancer.

Researchers have been evaluating the schedule and dosing of Aranesp in an effort to establish the fewest number of doses that maintain effectiveness. Fewer doses require less time for the patient and physician, fewer medical resources, and reduce pain and cost.

Aranesp was previously approved at a dose of once per week. It is now the only agent approved for every three-week dosing in the management of chemotherapy-induced anemia.

Researchers from France recently conducted a clinical trial to evaluate the use of Aranesp in patients with low-risk MDS (MDS that is considered to be the least aggressive and associated with the greatest survival). This trial included 62 patients with anemia who were treated with Aranesp.

71% of patients responded to treatment with Aranesp with an improvement in their anemia.
Of the 13 patients who had not responded to treatment with epoetin alfa, eight responded to subsequent treatment with Aranesp.
After a median of 40 weeks, 36 of 46 patients who responded to Aranesp continued to respond to Aranesp.
The researchers concluded that treatment with Aranesp significantly improves anemia in patients with low-risk MDS.

Reference: Mannone L, Gardin C, Quarre MC, et al. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodycplastic syndrome. Results of a phase II study. British Journal of Haematology. 2006;133:513-519.

Dacogen™ Approved for Myelodysplastic Syndromes

The United States Food and Drug Administration (FDA) has approved the agent Dacogen™ (decitabine) for the treatment of patients with myelodysplastic syndromes (MDS).

Myelodysplastic syndromes are a group of blood (hematologic) disorders that are diagnosed in 10,000 to 20,000 individuals annually in the U.S. MDS occurs when immature blood cells do not mature properly and are never able to perform their intended function. They instead crowd out normal blood cells in the bone marrow, often inhibiting other cells from performing their intended functions.

MDS can also develop into an aggressive form of leukemia, acute myelogenous leukemia (AML). Preventing or delaying the development of MDS into AML is an important consideration since long-term survival for AML is not favorable.

The different classifications of MDS range from low-risk to high-risk. Low-risk patients often have less aggressive disease that may be managed with blood transfusions (referred to as transfusion-dependent) or agents that stimulate red blood cell growth, such as Aranesp®. High-risk patients may need more aggressive management of their disease. Since blood transfusions are time consuming, require medical resources, increase medical costs, and are associated with the potential of infection, pain, and other reactions, reducing or preventing the need for the transfusions in patients with MDS is a major consideration.

The FDA approval for Dacogen was prompted by results of clinical trials demonstrating that it effectively improved outcomes in patients with MDS when compared to supportive care. Overall, Dacogen provided anticancer responses in approximately 17%-26% of patients in these trials—demonstrating a significant improvement over supportive care measures. These responses reduced the need for blood transfusions in a significant portion of patients.

Dacogen continues to be evaluated in clinical studies to provide further data on its potential in the treatment of MDS.

Patients diagnosed with MDS may wish to speak with their physician regarding their individual risks and benefits of treatment with Dacogen.

Reference: MGI Pharma. U.S. FDA Approves Dacogen(TM) (Decitabine) for Injection; Dacogen(TM) Approved for Patients with all FAB Classifications of MDS; Commercial Launch Planned For Late May. Available at: http://investors.mgipharma.com/phoenix.zhtml?c=73842&p=irol-newsArticle&ID=851140&highlight=. Accessed May 2006.