By Amy D’Orazio, PhD, B. Diane Gambill, PhD & Jennifer Klem, PhD

The mission of the American Society of Hematology (ASH) is to further the understanding, diagnosis, treatment, and prevention of disorders affecting the blood, bone marrow, and immune system by promoting research, clinical care, education, training, and advocacy in hematology.

The annual meeting, held each December, addresses new treatment options and their side effects for blood-related cancers such as leukemia, lymphoma, and myeloma.

Rituxan Improves Outcomes in Low-Grade Non-Hodgkin’s Lymphoma Several presentations at ASH were focused on newer applications of Rituxan® (rituximab), a monoclonal antibody that has improved the outcome of patients with lymphoma. An international trial compared standard CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy with or without Rituxan in patients with slow-growing, low-grade lymphoma. The addition of Rituxan to chemotherapy prolonged the quality and duration of remission in these patients. More specifically, the Rituxan group’s time to treatment failure was a median of 27 months versus seven months for the group on CVP alone.

A second trial conducted by the Eastern Cooperative Oncology Group (ECOG) in the United States gave additional doses of Rituxan after completion of CVP (also called maintenance Rituxan) and found this also improved the duration of remission in low-grade lymphoma patients. These two studies demonstrate that Rituxan can improve the efficacy of CVP chemotherapy in patients with low-grade non-Hodgkin’s lymphoma.

For more information about Rituxan, visit www.rituxan.com.

More Data Show Benefit of Rituxan in Aggressive Lymphoma
The addition of Rituxan improves the efficacy of standard chemotherapy treatment for patients with aggressive lymphoma. The benefit of adding Rituxan to CHOP chemotherapy was demonstrated in an American trial conducted by ECOG. Rituxan was helpful when given either with chemotherapy or after completion of chemotherapy. A European trial also demonstrated the benefits of adding Rituxan to CHOP in both older (age 60 and over) and younger (under 60) patients.

New Applications for Velcade in Myeloma and Lymphoma
In May 2003, the U.S. Food and Drug Administration approved Velcade® (bortezomib), made by Millennium Pharmaceuticals, for patients with advanced multiple myeloma who progressed despite treatment. Velcade represents an entirely new class of drugs called proteasome inhibitors. Proteasomes are the “digestive system” of the cell, breaking down and eliminating proteins made by the cell, including many of the proteins that control cell growth. Inhibiting the proteasome function with Velcade has been shown to shut down cell growth and, in many cases, lead to the death of cancer cells.

Two studies showed Velcade had activity in patients with lymphoma whose disease had progressed on multiple other therapies. Still more encouraging were the good responses seen in the subset of patients with mantle cell lymphoma, a rare and hard to treat subtype of lymphoma.

Clinical trials in mantle cell patients are currently ongoing. To learn about Velcade clinical trials, call 866-VELCADE (835-2233). And for more about Velcade, visit www.velcade.com.

Zarnestra Stops Leukemia
Ras, a common mutation found in multiple cancer types, became a logical target for the development of new cancer therapies. Zarnestra® (tipifarnib), an oral medication that inhibits an enzyme that activates Ras, is a new therapeutic agent undergoing evaluation for acute myelogenous leukemia (AML), the most common type of leukemia in adults, as well as in myelodysplastic syndrome (MDS), a disorder in which abnormal cells crowd out normal cells in the bone marrow.

For patients with AML or MDS, the abnormal cells in the bone marrow prevent normal, functional blood cells from forming and maturing, leading to complications such as severe anemia. A phase II trial showed Zarnestra reduced abnormal cells seen in MDS and AML patients, and the treatment was fairly well tolerated by these patients, most of whom were in their 70s.

Arsenic Trioxide Shows Promise in Many Blood Cancers
Arsenic trioxide has been used for centuries as a medicinal agent and has also been used as a traditional Chinese treatment for skin cancer. An intravenous preparation of arsenic trioxide (called Trisenox®) was approved in September 2000 in the United States for treatment of patients with a rare type of leukemia called acute promyelocytic leukemia, which affects 1,000-1,500 patients annually.

Studies reported at ASH suggest Trisenox may be helpful in patients with more common malignancies like multiple myeloma when given in combination with melphalan, an oral chemotherapy drug, and vitamin C.

Arsenic trioxide was also found to be of some benefit in a condition called myelodysplastic syndrome, a condition usually seen in older individuals, where the bone marrow fails to make enough white and red blood cells. These studies with arsenic trioxide, though preliminary, suggest this old medicine may find a number of novel uses. For more information on Trisenox, visit www.cticseattle.com.

New Results in the Fight Against Multiple Myeloma
Thalidomide was linked to serious birth defects in the 1950s when given to pregnant women as a sleeping pill. But today, Thalomid® (thalidomide) has been found to have significant benefit in a number of conditions, including multiple myeloma. Unfortunately, Thalomid has a number of side effects, including constipation, drowsiness, rash, and nerve damage.

Revlimid (CC-5013) is a novel derivative of thalidomide that appears to have more potent activity in both multiple myeloma and myelodysplatic syndrome. Revlimid, like thalidomide, is thought to work by increasing the ability of the immune system to attack tumor cells and stifle their ability to grow. Furthermore, Revlimid has a lower risk of side effects.

In a phase II study of patients with multiple myeloma whose disease had progressed despite several different treatment regimens, 38% responded to therapy with Revlimid. In a separate preliminary trial, anemic patients with myelodysplastic syndrome also responded to Revlimid.

To find clinical trials for Revlimid, visit www.clinicaltrials.gov and search for CC-5013, and for more information about Thalomid, go to www.celgene.com.