Leukemia, myeloma, VTE highlight ASH meeting

February 20, 2006

Research reported at the 47th Annual Meeting and Exposition of the American Society of Hematology, held recently in Atlanta, featured upbeat findings for a new multiple myeloma agent for leukemia patients and found evidence supporting much wider prophylaxis against venous thromboembolism.

Research reported at the 47th Annual Meeting and Exposition of the American Society of Hematology, held recently in Atlanta, featured upbeat findings for a new multiple myeloma agent for leukemia patients and found evidence supporting much wider prophylaxis against venous thromboembolism.

Patients with chronic myelogenous leukemia (CML) who respond well to imatinib (Gleevec, Novartis) treatment after 12 months may go on to even further eradication of disease after four years, according to an updated analysis of IRIS (International Randomized trial of Interferon/ara-C versus STI571), a trial that showed remarkable superiority for imatinib over interferon and ara-C.

"It's important to understand this concept that the higher the log reduction in transcripts," the fewer the number of transcripts in the individual person, stated hematology professor John Goldman, M.D., Imperial College, London, England. He noted that with a 2-log reduction in leukemia cells in response to imatinib detected through real-time quantitative PCR (polymerase chain reaction) analysis, patients become negative for the abnormal Philadelphia chromosome. At a 3-log reduction they have a major molecular response, and at about a 4.5-log reduction, no transcripts are detected.

"There is an optimistic possibility that the risk of disease progression might diminish with the passage of time," Goldman concluded.

Michael Fiegl, M.D., Medical University of Innsbruck, Austria, looked retrospectively at 108 chronic lymphocytic leukemia (CLL) patients with B-cell CLL treated with alemtuzumab (Campath, Berlex) at 25 centers in Austria to see whether they fared as well as those treated with alemtuzumab in prospective studies. While he found a lower overall response rate, therapeutic benefit occurred in more than half the patients, and overall survival was good at 15 months for those with three or more previous therapy lines and 20 months for all patients.

Median overall survival was not reached for those treated with fewer than three prior regimens. Fiegl noted that while mean patient age was higher than in prospective studies, survival was as good.

Combining alemtuzumab and rituximab (Rituxan, Genentech) for patients with relapsed/refractory CLL, stated associate professor Stefan Faderl, M.D., MD Anderson Cancer Center, Houston, is based on their respective strengths: Alemtuzumab clears bone marrow (but not bulky lymph nodes), and rituximab treats lymph nodes (but not bone marrow). In prior experience with bolus alemtuzumab and rituximab, overall response was 52%. Testing whether alemtuzumab given via continuous outpatient 24-hour infusion (15 mg/ 24 hours x 6 days) followed by subcutaneous injections (30 mg) twice a week for three cycles would offer benefit in better targeting CD52 and CD20 cell surface antigens associated with shorter survival, investigators treated 33 patients (24 evaluable).

The overall response rate was similar, but the complete response rate for continuous infusion was superior to that reported for bolus alemtuzumab. Treatment was well tolerated. Faderl said he wants to test this administration route at earlier CLL stages.

Studies of the combination of lenalidomide (Revlimid, Celgene) and dexamethasone (Rev/Dex) in multiple myeloma are encouraging. Lenalidomide, a novel thalidomide derivative affecting multiple intracellular biological pathways, is demonstrating efficacy in both newly diagnosed and in relapsing or refractory multiple myeloma patients.

In the United States, about 80% of newly diagnosed multiple myeloma patients who are candidates for stem cell transplants receive the combination of thalidomide and dexamethasone (Thal/Dex), stated S. Vincent Rajkumar, M.D., Mayo Clinic. The difficulty with Thal/Dex has been high nonhematological side effects, occurring at grade 3 or higher in 67% of patients in the Eastern Cooperative Oncology Group (ECOG) trial.

Rajkumar's study of 34 patients receiving Rev/Dex revealed objective responses in 91% of patients, with 38% having a very good partial response or better. Over the entire course of therapy, grade 3-4 hematologic toxicities were found in 21% of patients. "We showed that lenalidomide/dexamethasone is a highly effective oral regimen for newly diagnosed multiple myeloma," he said.