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What's New In Research - July 17, 2003
The quality of evidence supporting treatment recommendations for multiple myeloma is modest, at best.
(c) Copyright 2003 Hematology Week via NewsRx.com

"We have done a systematic review of all randomized studies in myeloma, identified through a comprehensive search," scientists in the United States report.

"Our aim was to investigate and critically examine the effects of various treatment modalities on outcome in patients with multiple myeloma and address 22 specific clinical questions in the management of this disease. As a result of our analysis we identified two therapeutic advances in the management of myeloma that, according to the evidence, are most important for improving outcome," wrote A. Kumar and colleagues, University of South Florida, H. Lee Moffit Cancer Center & Research Institute.

"These advances were: introduction of high dose chemotherapy, which appears to be superior to conventional chemotherapy, and the use of bisphosphonates, which decrease the probability of pathological vertebral fractures," the researchers wrote.

"However, the overall quality of the body of evidence for myeloma management was poor. Many trials were done with small sample sizes, and did not include reporting power analysis," they added.

The researchers concluded: "The majority of studies had inadequate allocation concealment, and few were analyzed according to intention to treat principle. We conclude that the quality of total evidence supporting treatment recommendations in myeloma is modest at best and has an ample scope for improvement."

Kumar and colleagues published their study in Lancet Oncology (Management of multiple myeloma: a systematic review and critical appraisal of published studies. Lancet Oncol, 2003;4(5):293-304).

For more information, contact B. Djulbegovic, University of South Florida, H. Lee Moffit Cancer Center & Research Institute, Interdisciplinary Oncology Program, 12902 Magnolia Dr., Tampa, FL 33612, USA.

Kirin to Push Forward Cancer Cell Angiogenesis Inhibitor Study.
(c) 2003 The Chemical Daily Co., Ltd.

Kirin Brewery has revealed the intention to tackle the development of a cancer cell angiogenesis inhibitor; cancer immunotherapy using dendritic cells (DC) is progressing satisfactorily in the U.S. Kirin has identified cell therapy and antibody drugs as one its core areas, and Dendreon (U.S.) has licensed it cancer therapy using dendritic cells.

Dendreon has recently been given FDA approval for phase-III clinical trials in the U.S. for the treatment of prostate cancer. The therapy, if approved, would be the world's first cancer cell therapy. Kirin previously developed cancer cell angiogenesis inhibitor KRN 633, and later KRN 951, planning to launch clinical tests in or after 2004.

Kirin has applied for approval of the Ministry of Health, Labour and Welfare to manufacture CD34 positive cell separator AM9802 as a medical device and is expecting to be given approval by the year-end.

A dendritic cell (DC) is considered to play a pivotal role in immuno responses and the firm is pursuing the development of a vaccine using the cells. Under a partnership with Dendreon, Kirin is also conducting clinical development of prostate cancer treatment (APC 8015 in clinical tests in Japan) and the treatment of multiple myeloma (APC 8020 in phase-I clinical tests), both using DCs.

APC 8020 is Japan's first therapeutic cell product to be clinically applied. In the U.S., on the other hand, FDA gave Dendreon a special protocol assessment status for phase-III tests, allowing APC 8015 administration depending on the development of the target cancer. It will be used for pivotal study of 275 patients with androgen-non-dependant prostate cancer.

Prothrombotic environments may foster embolisms in multiple myeloma patients.
(c) Copyright 2003, Drug Week via NewsRx.com

"Venous thromboembolism (VTE) is a major complication in patients with multiple myeloma (MM) during treatment with thalidomide combined with chemotherapy and/or dexamethasone. The pathophysiology is not clear. We performed a cross-sectional study in 20 MM patients who were treated with thalidomide for refractory/relapsed disease," scientists in Netherlands report.

"Seven patients (35%) experienced an episode of VTE. Plasma samples were analyzed for known risk factors for VTE and compared with those from 30 MM patients without thalidomide treatment. The patients groups differed in their baseline characteristics in activity status only," noted M.C. Minnema and colleagues, University of Utrecht, Medical Center.

"Extremely high levels of factor VIII-coagulant activity (FVIII:C, mean 352%) and von Willebrand factor antigen (VWF-Ag, 374%) were found in all patients using thalidomide. All other prothrombotic risk factors were normal."

"In patients with VTE, VWF-Ag but not FVIII:C levels were significantly higher as compared with patients without VTE. Patients without thalidomide treatment had significantly lower levels of both coagulation factors but the difference was only due to difference in activity status," said researchers.

"High FVIII:C/VWF-Ag levels are found in patients with active MM and this is probably a reflection of increased bone marrow angiogenesis in MM. These prothrombogenic circumstances could contribute to the high incidence of WE during treatment with thalidomide in combination with dexamethasone/chemotherapy," Minnema and coauthors concluded.

Minnema and colleagues published their study in Journal of Thrombosis and Haemostasis (Extremely high levels of von Willebrand factor antigen and of procoagulant factor VIII found in multiple myeloma patients are associated with activity status but not with thalidomide treatment. J Thromb Haemost, 2003;1(3):445-449).

For more information, contact H.M. Lokhorst, University of Utrecht, Medical Center, Department of Hematology, HP G03647, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.

Peripheral blood stem cell (PBSC) transplantation can be highly effective for multiple myeloma patients.
(c) Copyright 2003 Hematology Week via NewsRx.com

In a study from Italy, "a total of 30 multiple myeloma patients" received PBSC grafts "from HLA-identical siblings."

The "time to transplantation was 3-107 months (median 8)," noted I. Majolino and coauthors at Azienda Ospedaliera S. Camillo-Forlanini in Rome. "Prior chemotherapy times varied from one to six months (median one)."

"Four patients were in complete remission (CR), 11 in partial remission (PR), 13 were considered to be nonresponders, and two had progressive disease," the scientists wrote. "Most were conditioned with busulfan-melphalan. PBSC were collected by apheresis after G-CSF [granulocyte colony-stimulating factor] or sequential GM-CSF [granulocyte-macrophage colony stimulating factor] and G-CSF."

"The patients were grafted with 4.4-24.1 x 106/kg CD34+ (median 7.9) and 0.9-7.9 x 108/kg CD3+ cells (median 2.3)," according to the report. "GVHD prophylaxis was methotrexate-cyclosporine."

"Engraftment was complete and rapid. Grades II-IV acute GVHD (aGVHD) developed in 16 (53%), but was grade III-IV only in five (17%); chronic GVHD (cGVHD) developed in 17 out of the 24 evaluable patients (71%)," study data showed. "A total of 18 patients (71%) attained CR after transplantation. TRM [transplant-related mortality] was 30% overall, 16% at 100 days."

"There was only one relapse. Overall survival and event-free survival at 73 months were 60% and 67%, respectively," the report indicated. "PCR negativity for IgH-gene rearrangement occurred in all persistently CR patients studied."

"PBSC allograft can induce long remissions, because of profound suppression of the neoplastic clone that is probably linked to the antitumor effect of cGVHD," the researchers concluded.

Majolino and colleagues published their study in Bone Marrow Transplantation (High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors. Bone Marrow Transplant, 2003;31(9):767-773).

Additional information can be obtained by contacting I. Majolino, Azienda Ospedaliera S. Camillo-Forlanini, Hematology and Bone Marrow Transplantation Unit, Circonvallaz Gianicolense 87, I-00152 Rome, Italy.

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