http://journals.lww.com/oncology-times/Fulltext/2010/02101/M… Oncology Times: 10 February 2010 - Volume 32 - Issue 3 - pp 21-22 doi: 10.1097/01.COT.0000368433.81044.e7 News Myeloma: New Drug Roundup Carlson, Robert H.
NEW ORLEANS—Many new agents were discussed at the ASH Annual Meeting, of course, but one expert saw a trend in the presentations on new treatments for multiple myeloma.
“We saw investigators looking at the treatment paradigm all the way from smoldering myeloma through induction, consolidation, transplant, and ultimately long-term remission, to see where these new drugs are going to find an appropriate niche,” said Brian G.M. Durie, MD, Chairman and Medical Director of the International Myeloma Foundation and attending physician at Cedars-Sinai Medical Center in Los Angeles.
Activating Osteoblasts in Myeloma Treatments for bone disease in patients with multiple myeloma tend to concentrate on reducing activity of osteoclasts. But taking a different approach is BHQ880, a novel osteoblast-activating anti-DKK1 human monoclonal antibody that allows bone remodeling inhibited by myeloma. “This human monoclonal antibody has a very specific target, TKK1, and this target essentially is the culprit for not allowing bone remodeling to occur in multiple myeloma,” explained Swaminathan Padmanabhan, MD, of the Institute for Drug Development, Cancer Treatment and Research Center, at the University of Texas Health Science Center at San Antonio.
He said BHQ880 is unlike the bisphosphonates, which add calcium back to bone to prevent bony destruction but don't address the bone formation issue: “For the first time a drug is addressing the bone formation problem, which I think is a fundamental issue in the bone disease in multiple myeloma.”
He presented results of a multi-institution BHQ880 Phase I/II study in relapsed and refractory multiple myeloma that included 34 patients, receiving BHQ880 on the first day of a 21-day schedule, followed by the bisphosphonate zoledronic acid on Day 2 and antimyeloma therapy with lenalidomide and/or dexamethasone on Day 3 (but not bortezomib, which has bone-anabolic properties).
“The zoledronic acid decreases bone resorption, and BHQ880 increases new bone formation, so this combination, along with an antimyeloma drug, may provide an effective treatment strategy for multiple myeloma bone disease,” Dr. Padmanabhan said. Seven of the 34 patients have relapsed disease and four have refractory disease. Among the 11 patients evaluable for safety there has been no infusion-related toxicity so far, Dr. Padmanabhan said, and no toxicities related to the drug. One patient still receiving BHQ880 is currently in the ninth cycle.
“Dexa scans have shown positive increases in bone mineral density in several of the patients, with changes ranging from +.02% to +6.0%, in as early as three months,” Dr. Padmanabhan said. But there has been no evidence that BHQ880 has any effect on the myeloma disease. The Phase II portion of the study was expected to begin early this year. Dr. Durie said in a telephone interview after the meeting that he was familiar with the development of BHQ880, stemming from work in gene expression profiling by John D. Shaughnessy, Jr., PhD, Professor of Medicine at the University of Arkansas. There has been a lot of drug development work on shutting down osteoclasts, Dr. Durie said, calling BHQ880 a very interesting approach to the problem of getting increased activity of osteoblasts to have bone healing. xxxxxxxxxxxxxxxxx
Ab wann rührt Novartis die Trommel für diesen HuCAL-Antikörper? |