Multiple Myeloma

This special “Annual Highlights” supplement to Oncology NewsInternational is a compilation of the major advances in the managementof the lymphomas and leukemias during 2002, as reported in ONI.Commentaries by the editors, Drs. Gregory Bociek, James Armitage,and Michael Keating, provide perspective and prediction as to howthese developments may affect clinical practice.

PHILADELPHIA-Early reports of the efficacy of thalidomide (Thalomid) as initial therapy for multiple myeloma have been confirmed by researchers at The University of Texas M.D. Anderson Cancer Center, Donna Weber, MD, reported at a symposium sponsored by the University of Pennsylvania and the Multiple Myeloma Research Foundation.

CAMBRIDGE, Massachusetts-Millennium Pharmaceuticals, Inc. has begun a pivotal phase III clinical trial of Velcade (bortezomib) (formerly known as MLN341, LDP-341, and PS-341) in patients with multiple myeloma. Velcade is designed to block proteasomes, enzyme complexes in the cell responsible for breaking down a variety of proteins, including many that regulate cell division, the company said in a press release.

LITTLE ROCK-Deletion of chromosome 13 and hypodiploidy are major independent predictors of poor prognosis in multiple myeloma, according to a study involving close to 1,500 multiple myeloma patients (ASCO abstract 1054). "Chromosomal studies are the most important prognostic factor in the treatment of myeloma," said lead investigator Guido J. Tricot, MD, PhD, head of the Academic Division of Myeloma Transplant, Myeloma Institute for Research and Therapy, at the University of Arkansas for Medical Sciences in Little Rock. "Chromosome 13 deletion and hypodiploidy are associated with poor prognosis, but too many institutes are failing to do these studies which can predict outcome and help customize treatment."

CAMBRIDGE, Massachusetts-The proteasome inhibitor PS-341 produced objective durable responses in multiple myeloma patients with relapsed and refractory disease in a phase II multicenter trial (ASCO abstract 40). "The activity of the

CLEVELAND-Hospitalizations due to adverse events were less likely to occur among newly diagnosed multiple myeloma patients who received DVd (pegylated liposomal doxorubicin [Doxil]/vincristine/dexamethasone (than those who received VAd (vincristine/doxorubicin [Adriamycin]/reduced-dose dexamethasone). Early results from a randomized phase III trial were reported by Mohamad A. Hussein, MD, of the Cleveland Clinic. The data are very preliminary, as safety data could be collected on only 94 of 135 patients who are enrolled at 22 sites in the study (ASCO abstract 1107).

LITTLE ROCK-"For the first time, we have shown that with increasing age, the number of stem cells mobilized decreases," said Guido J. Tricot, MD, PhD, reporting the results of a multiple myeloma study (ASCO abstract 1055). Clinicians can

Bedford Laboratories announced that it has received approval from the Food and Drug Administration to market pamidronate disodium for injection. The product will be the only liquid version available on the market, and is equivalent to the Novartis pamidronate disodium product (Aredia), a bone resorption inhibitor indicated for the treatment of hypercalcemia associated with malignancy, for Paget’s disease, and for osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma.

EAST HANOVER, New Jersey-The US Food and Drug Administration has approved the Novartis drug Zometa (zoledronic acid for injection) for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.

ORLANDO-The proteasome inhibitor MLN341 (formerly known as LDP-341 and PS-341) shows evidence of safety, biologic activity, and antitumor activity in the treatment of multiple myeloma, according to preliminary analysis of a phase II trial, Paul G. Richardson, MD, said at the 43rd Annual Meeting of the American Society of Hematology (abstract 3223). [The proteasome is an intracellular enzyme present in the cytoplasm and nucleus.]

The US Food and Drug Administration (FDA) has approved zoledronic acid (Zometa) for the treatment of bone complications in patients with multiple myeloma and patients with solid tumors, in conjunction with standard antineoplastic therapy.

ROCKVILLE, Maryland-Members of the Oncologic Drugs Advisory Committee (ODAC) have unanimously recommended that the Food and Drug Administration approve Zometa (zoledronic acid for injection, Novartis) for the treatment of bone metastases in patients with multiple myeloma and breast cancer, prostate cancer, lung cancer, and other solid tumors.

HOUSTON-The farnesyl transferase inhibitor R115777 (tipifarnib, also known as Zarnestra) produced an overall response rate of 33% in patients with chronic myelogenous leukemia (CML) and decreased splenomegaly in most patients with myelofibrosis, but was not effective in multiple myeloma, reported Deborah Thomas, MD, at the 43rd Annual Meeting of the American Society of Hematology. Dr. Thomas is assistant professor in the Department of Leukemia at The University of Texas M. D. Anderson Cancer Center in Houston.

SEATTLE-A two-stage procedure that combines high-dose chemotherapy with autologous stem cell transplantation (SCT) with an immunosuppressive (but not myeloablative) allogeneic SCT in multiple myeloma improves complete response rate and decreases treatment-related mortality.

BETHESDA, Maryland-A National Cancer Institute (NCI) panel, which explored how to improve survival among leukemia, lymphoma, and myeloma patients and stem the soaring death rates for those with non-Hodgkin’s lymphoma and multiple myeloma, has recommended giving priority to 10 areas of research.

ORLANDO-Encouraging preliminary clinical results have paved the way for phase II trials of a novel oral therapy for multiple myeloma. The study, under the leadership of Paul G. Richardson, MD, instructor in medicine, Harvard Medical School, evaluated the safety and efficacy of the immunomodulatory drug (IMiD) CC5013, a thalidomide derivative. He presented the findings at the 43rd annual meeting of the American Society of Hematology (abstract 3225).

CHICAGO-Eight out of nine patients with advanced multiple myeloma responded to LDP-341, a proteasome inhibitor formerly called PS-341, during a phase I clinical trial in patients with advanced hematologic malignancies, according to preliminary results reported at the American Chemical Society’s annual meeting.

NEW CANAAN, Connecticut-The Multiple Myeloma Research Foundation (MMRF) has announced the recipients of the first MMRF Collaborative Program Grant, which is funding $1.5 million over 3 years to three centers of excellence in myeloma

Sen. Kay Bailey Hutchison (R-Tex) is supporting a bill that would authorize the National Cancer Institute (NCI) to increase research on blood cancers, particularly leukemia, lymphoma, and multiple myeloma. The Senate Health, Education, Labor,

EAST HANOVER, NJ-In a news release, Novartis announced that the FDA has granted priority review to its intravenous bisphosphonate Zometa (zoledronic acid for injection) for the treatment of bone metastases associated with a broad range of tumor types, including multiple myeloma and prostate, lung, and breast cancer. The application is based on data from three large international clinical trials evaluating more than 3,000 patients. Zometa previously received FDA approval for use in treating tumor-induced hypercalcemia.

The third edition of the Color Atlas of Clinical Hematology, authored by Drs. A. Victor Hoffbrand and John E. Pettit, contains 19 chapters covering the entire spectrum of hematology, including normal hematopoiesis, benign and malignant

ROCHESTER, Minnesota-In a study of thalidomide (Thalomid) for early-stage multiple myeloma, 6 of 16 patients had a confirmed response-50% or greater reduction in serum and urine monoclonal (M) protein. S. Vincent Rajkumar, MD, and his colleagues at the Mayo Clinic reported the interim finding in Leukemia (8:1274-1276-2001).

SAN DIEGO, California-Few studies have addressed the psychological effect of multiple myeloma, even though the disease has a discouraging prognosis and is often associated with significant pain. To learn more about this issue, Angela Poulos, RN, CNS, MS, a clinical nurse specialist in radiation oncology at the Mayo Clinic, examined the link between pain, mood disturbance, and quality of life (QOL) in these patients.

Researchers at Cedars-Sinai Medical Center report that very low doses of a potent new bisphosphonate, zoledronic acid (Zometa), reduces the complications arising from multiple myeloma and breast cancer that have metastasized to the bone. The

At the Chemotherapy Foundation Symposium XVIII in New York City, researchers from the Arkansas Cancer Research Center, Cedars-Sinai Medical Center, M. D. Anderson, and the National Cancer Institute presented updated clinical trial data

SAN ANTONIO-Zoledronic acid (Zometa), a high-potency bisphospho-nate, is at least as effective as pamidronate (Aredia) in treating bone metastases, James R. Berenson, MD, said at the 23rd Annual San Antonio Breast Cancer Symposium. Delivered in a 5-minute infusion, zoledronic acid is expected to be more convenient and easier to use than the older bisphosphonate, said Dr. Berenson, director, Multiple Myeloma and Bone Metastasis Programs, Cedars-Sinai Medical Center, Los Angeles.

Laboratory studies evaluating the activity of Celgene’s immunomodulatory drugs (IMiDs) on multiple myeloma cells suggest that these agents may be beneficial in the treatment of multiple myeloma. Researchers from the Dana-Farber Cancer Institute

The anti-CD20 chimeric monoclonal antibody rituximab (Rituxan) has been successfully used in the treatment of many B-cell malignancies. Clonotypic B cells circulating in multiple myeloma (MM) patients express CD20, and it has been suggested

SAN FRANCISCO-Seven years seems to be the cutoff point for multiple myeloma patients receiving tandem autotransplants to avoid relapse and achieve long-term survival. "Most relapses were seen in the first 3 years," Guido Tricot, MD, said at the American Society of Hematology (ASH) 42nd Annual Meeting. "Relapses start to decrease between 3 and 7 years. After 7 years, it is exceptional to relapse."

SAN FRANCISCO-Multiple myeloma patients receiving intensive chemotherapy following bone marrow transplantation had "significantly superior" survival, according to a poster presentation at the American Society of Hematology (ASH) 42nd Annual Meeting. The survival advantages extended to patients with two or more risk factors for relapse after high-dose therapy.