By Amy D’Orazio, PhD

Leukemia

Arranon, A New Active Agent

The Oncologic Drugs Advisory Committee (ODAC) of the Food and Drug Administration voted in favor of the accelerated approval of Arranon® (nelarabine) on Sept. 14 for the treatment of T-cell acute lymphoblastic leukemia, or T-ALL, and T-cell lymphoblastic lymphoma in adults and children. Though the FDA makes the final decision on drug approval, the agency typically follows ODAC’s recommendation.

In adult patients, T-ALL is difficult to treat, especially once it has relapsed. The committee’s recommendation came in part from results of a phase II trial of Arranon that showed remission in 23 percent of patients, even though most of the patients had undergone two or more prior treatments. The remissions persisted for an average of 10 months, and 40 percent of patients were disease-free for at least one year.

Arranon is inactive until converted to its active, toxic form that inhibits cell division. This mechanism of action reduces side effects while concentrating its toxic effects on the tumor by shutting down the machinery for cell growth and division. Common side effects include reduced blood counts, fatigue and infection. For more on Arranon, visit www.gsk.com.

Blood Transfusion

Iron Overload Relief for Transfusion Patients

Anemia, a common cancer symptom and treatment side effect, is often treated with red blood cell transfusions. But patients who receive frequent transfusions may become overloaded with iron. Over time, iron deposited in important organs, such as the liver, pancreas and heart, leads to loss of function and permanent damage. To clear the body of excess iron, physicians have relied on agents such as Desferal® (deferoxamine), an injectable agent infused for eight to 12 hours a day for five to seven days a week. These older agents were not only inconvenient but also had a variety of side effects that required close monitoring.

A new agent called Exjade® (deferasirox) has the advantage of being taken by mouth once a day. In trials of more than 1,000 patients, including head-to-head comparisons with Desferal, Exjade effectively reduced iron overload in adult and pediatric transfusion patients. The Food and Drug Administration is currently evaluating Exjade for approval under its priority review program. For details, visit www.novartis.com.

Myelodysplastic Syndromes

Revlimid Tames Transfusion-Dependent MDS

By a vote of 10 to 5 in mid-September, the Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) recommended full approval of Revlimid® (lenalidomide) for treating myelodysplastic syndromes (MDS).
MDS encompasses a variety of blood disorders in which abnormal blood cells crowd out normal blood cells, reducing their ability to function properly. Because severe anemia is common in MDS, patients tend to become dependent upon blood transfusions. Researchers recently learned some MDS cases are characterized by a specific gene abnormality, known as the 5q deletion, found in as many as 18 to 25 percent of MDS patients. This genetic fingerprint is important because patients with this marker are less likely to respond to certain therapies and are more likely to develop acute leukemia. ODAC’s approval recommendation is specifically for patients with the 5q deletion.

The committee based its recommendation on a trial of 148 transfusion-dependent MDS patients—all of whom had the 5q deletion (alone or in combination with an additional chromosomal abnormality)—66 percent became transfusion-independent for a median of more than 47 weeks. For many, resolution of anemia became apparent within one month of treatment, and 70 percent of patients had a temporary return to normal genetics of their circulating cells (a cytogenetic response). More recent studies with Revlimid have demonstrated clinical benefit in low- to intermediate-risk patients who lack a distinct genetic abnormality. Revlimid, an immunomodulatory drug, is also being studied in multiple myeloma, metastatic melanoma and chronic lymphocytic leukemia. For more information on Revlimid, visit www.celgene.com.