Mayo Clinic study on vertebroplasty shows reduced back pain

A Mayo Clinic study has found patients report less back pain at rest and while active following vertebroplasty, a procedure in which medical cement is injected into painful compression fractures in the spinal vertebrae due to osteoporosis. Patients also reported improved function in their daily activities, such as walking, housework and getting dressed. The findings are published in the November/December issue of American Journal of Neuroradiology, http://www.ajnr.org.

"These findings give us as good evidence as there is -- in a study without a group receiving another or no treatment for comparison -- that patients are more functional for up to a year after vertebroplasty than before vertebroplasty," says David Kallmes, M.D., the Mayo Clinic neuroradiologist who led the study.

The investigators conducted the study to assess vertebroplasty with a well-validated questionnaire specifically designed to measure back pain, the Roland-Morris Disability Questionnaire (RDQ). They reviewed records of 113 Mayo Clinic vertebroplasty patients. Of this group, RDQ scores were available for 108 patients before vertebroplasty treatment, and after treatment for 93 patients at one week, 73 patients at one month, 46 patients at six months and 15 patients at one year. Patients' pain during rest and activity improved an average of seven points one week after treatment and remained improved one year following vertebroplasty. Prior to treatment, the average RDQ score was 18 on a scale of 23. The RDQ dropped to an average score of 11 immediately after treatment and remained at that level throughout the study.

Dr. Kallmes explains that in light of the wide practice of vertebroplasty for vertebral compression fractures, a study using a top-caliber back pain measurement tool like the RDQ was critical, especially in light of the often subjective nature of pain reporting by different patients.

"It's hard to remember your pain," he says. "Also, it's hard to say how bad my pain is compared to your pain. I've had patients say their pain is no better after treatment, yet I look at them and they look 10 times better."

Dr. Kallmes explains that ultimately, vertebroplasty needs evaluation through a study of the highest quality, a clinical trial in which patients are randomly assigned to receive treatment or no treatment and in which the patients and investigators are blinded to which patients receive the real treatment or a placebo used for comparison.

"Vertebroplasty has been promulgated by physicians who performed the procedure without quantifying the benefit," he says. "Yet, medical literature is rife with studies that have debunked therapies that are already in use."

Dr. Kallmes is making strides toward high-quality measurement of vertebroplasty. Currently, he is leading an international, multicenter study looking at whether the cement used in vertebroplasty is responsible for the pain relief reported by patients. Patients in this study are randomly assigned to receive treatment with the real cement used in vertebroplasty or a placebo.

Patients for whom vertebroplasty is appropriate, according to Dr. Kallmes, have osteoporosis or a similar condition and have suffered compression of their spines with no or minimal injury. For example, while bending over to tie their shoes or turning over in bed, patients' vertebrae may fracture because their bones are weakened due to osteoporosis. Each year, 700,000 people suffer this injury. For four out of five patients, the fracture heals and the accompanying pain goes away in approximately four weeks with bed rest and analgesics. However, for one in five patients, the fracture does not heal and the pain persists, requiring treatment. Surgery is not an option for these patients, as their bones are too weak. Vertebroplasty is the only available treatment option for patients in this condition.

Vertebroplasty is not appropriate for patients with back pain due to ligament injuries, joint disease or narrowing of the spinal canal, says Dr. Kallmes.

For more on vertebroplasty, see http://www.mayoclinic.org/vertebroplasty/index.html.

Weill Cornell team Identifies Trigger for Relapse

Here's a wonderful Christmas present for Myeloma patients.
***
Cyclin-Kinase Pairing Is Crucial to Oncogenesis

Findings Point to New Drug Targets

NEW YORK (December 23, 2005) — In a breakthrough discovery, researchers at Weill Medical College of Cornell University believe they have pinpointed the mechanism that triggers relapse in patients with deadly multiple myeloma.

While available drugs can push the disease into temporary remission, fatal, uncontrolled cell division always re-emerges over time. Until now, the cellular mechanism driving this relapse has remained unclear.

"We found that specific pairings of cell-cycle regulators — proteins called cyclins and enzymes called kinases — are necessary to drive myeloma cells toward that state of uncontrolled cell division, a hallmark of cancer," explained senior researcher Dr. Selina Chen-Kiang, Professor of Pathology and Laboratory Medicine, and Professor of Microbiology and Immunology at Weill Cornell Medical College.

"This discovery runs counter to the previous dogma that the overexpression of a particular cyclin, called cyclin D1, was all that was needed to trigger the overproliferation of myeloma cells," added co-lead researcher Dr. Scott Ely, Associate Professor of Clinical Pathology and Laboratory Medicine at Weill Cornell.

Instead, the researchers found that cyclin D1 or a related regulatory protein, cyclin D2, must first pair up with specific kinase enzymes — called CDK 4 and CDK6 — to drive myeloma cells toward division.

"It's as if the cyclin molecule is the gas, and the enzyme is the engine. You need both to get the car going," Dr. Chen-Kiang said. "Now that we think we understand this relationship, we have a whole new opportunity to target drugs toward these enzymes, giving new hope for more effective treatments."

The findings were presented at this month's annual meeting of the American Society of Hematology, and are also published in the December 15 issue of Cancer Research.

Multiple myeloma originates deep in the bone marrow and is the second most common blood cancer. The disease is always fatal, with an average life expectancy after diagnosis of just three years. "There are drugs that are geared to getting people into remission, but they ultimately fail because there are still cancer cells that have the potential for self-renewal — they'll rise again and start dividing," Dr. Chen-Kiang explained.

Research continues as to why these myeloma cells don't undergo programmed cell death (apoptosis) as they should. But the Weill Cornell team focused on the other side of the cancer paradigm: Why these cells suddenly begin dividing uncontrollably.

Using bone marrow myeloma cells freshly isolated from patients and tumor cell lines obtained from end-stage patients, they discovered that this overproliferation hinges on specific cyclin-kinase relationships that govern cell cycling. These pairings appear to be mutually exclusive.

"For example, cyclin D1 pairs up with the enzyme CDK4, or cyclin D2 pairs up with CDK6 — but when we examined the cells, the two pairings never occurred together," said co-lead researcher Dr. Maurizio Di Liberto, Assistant Research Professor of Pathology and Laboratory Medicine at Weill Cornell.

The cyclin D2/CDK6 combo was particularly deadly, the team found.

"All of the cell lines that we obtained from terminal, end-stage patients showed this pairing," said Dr. Chen-Kiang. "That's exciting, because it suggests that we might be able to use the presence or absence of these biochemical pairings as prognostic indicators, which would help guide treatment."

She believes the findings should also overturn the old notion that the chromosomal translocation (and resultant overexpression) of cyclin D1 was the prime mover behind multiple myeloma.

"It never made sense to me — it was like having the gas without the engine," Dr. Chen-Kiang said. "Studies in Europe even found that patients with translocated cyclin D1 did better than patients without this translocation, giving us another reason to assume there was more going on there than meets the eye."

The finding could also have implications beyond multiple myeloma.

"It illuminates the complexity of how cancer arises," Dr. Ely said. "This finding is unprecedented in any cancer, and might apply to other malignancies — people just haven't looked at this hard enough before."

According to Dr. Chen-Kiang, finding compounds that target CDK4 and CDK6 are obvious next steps in the search for more effective treatments against multiple myeloma.

"It's still early," she said, "but a better understanding of how relapse occurs means that someday we may be able to prevent it from occurring at all."

This study was funded by grants from the National Institutes of Health and the Leukemia and Lymphoma Society.

Co-researchers included Dr. Ruben Niesvizky, Dr. Linda B. Baughn, Dr. Hearn J. Cho, Dr. Eunice N. Hatada, Dr. Daniel M. Knowles, and Dr. Joseph Lane — all of Weill Cornell Medical College in New York City.

Source: http://global.med.cornell.edu/news/wcmc/wcmc_2005/12_23_05.shtml

FDA grants REVLIMID approval for MDS

Celgene Corporation announced that the FDA granted approval of REVLIMID (lenalidomide) which is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. REVLIMID will be available through a REVLIMID Education and Prescribing Safety Program, called RevAssist(SM) via contracted pharmacies.

The safety profile for REVLIMID has shown that neutropenia and/or thrombocytopenia were the most common adverse event (AE) and that patients may require a dose adjustment. Other observed and common AE's include diarrhea, pruritis, rash, fatigue, constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain, peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea, and pharyngitis.

The timing of this approval will result in most initial shipments of REVLIMID to be distributed in early 2006.

SAFETY NOTICE:

REVLIMID(R) (lenalidomide) Capsules 5 mg & 10 mg

     WARNING: POTENTIAL FOR HUMAN BIRTH DEFECTS.

LENALIDOMIDE IS AN ANALOGUE OF THALIDOMIDE. THALIDOMIDE IS A KNOWN HUMAN TERATOGEN THAT CAUSES SEVERE LIFE-THREATENING HUMAN BIRTH DEFECTS. IF LENALIDOMIDE IS TAKEN DURING PREGNANCY, IT MAY CAUSE BIRTH DEFECTS OR DEATH TO AN UNBORN BABY. FEMALES SHOULD BE ADVISED TO AVOID PREGNANCY WHILE TAKING LENALIDOMIDE. BECAUSE OF THIS POTENTIAL TOXICITY AND TO AVOID FETAL EXPOSURE TO REVLIMID(R) (lenalidomide), IT IS ONLY AVAILABLE UNDER A SPECIAL RESTRICTED DISTRIBUTION PROGRAM. THIS PROGRAM IS CALLED "REVASSIST(SM)." UNDER THIS PROGRAM, ONLY PRESCRIBERS AND PHARMACISTS REGISTERED WITH THE PROGRAM ARE ALLOWED TO PRESCRIBE AND DISPENSE THE PRODUCT. IN ADDITION, PATIENTS MUST AGREE TO COMPLY WITH THE REQUIREMENTS OF THE REVASSIST(SM) PROGRAM TO RECEIVE DRUG.

WARNING:

HEMATOLOGICAL TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA)

LENALIDOMIDE IS ASSOCIATED WITH SIGNIFICANT NEUTROPENIA AND THROMBOCYTOPENIA. PATIENTS SHOULD HAVE THEIR CBC CHECKED WEEKLY FOR THE FIRST 8 WEEKS OF REVLIMID(R) (lenalidomide) TREATMENT AND AT LEAST MONTHLY THEREAFTER TO MONITOR FOR CYTOPENIAS. MOST DELETION 5q MDS PATIENTS STUDIED REQUIRED A DOSE ADJUSTMENT FOR NEUTROPENIA AND THROMBOCYTOPENIA.

WARNING: DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

REVLIMID(R) (LENALIDOMIDE) HAS DEMONSTRATED SIGNIFICANT RISK OF DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM IN SOME PATIENTS WITH CERTAIN MEDICAL CONDITIONS.

IMPORTANT SAFETY INFORMATION

Hypersensitivity: REVLIMID(R) (lenalidomide) is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components.

Other adverse events: Other most frequently reported adverse events were diarrhea, pruritis, rash, fatigue, constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain, peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea, and pharyngitis. REVLIMID(R) (lenaliodomide) is substantially excreted by the kidney, so the risk of toxic reactions may be greater in patients with impaired renal function.

About REVLIMID(R)

REVLIMID is a member of a proprietary group of novel IMiDs(R), immunomodulatory drugs. Celgene continues to evaluate treatments with REVLIMID for a broad range of hematology and oncology conditions. The IMiD pipeline, including REVLIMID, is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of-matter and use patents.

About RevAssist(SM)

FOR FURTHER INFORMATION ABOUT REVLIMID(R) AND THE RevAssist(SM) PROGRAM, YOU MAY GO TO THE INTERNET AT http://www.REVLIMID.com OR BY CALLING THE MANUFACTURER'S TOLL FREE NUMBER 1-888-4CELGENE. RevAssist(SM) is a proprietary risk-management restrictive distribution program, tailored specifically for REVLIMID patients, to prevent the potential for human birth defects and ensure prompt and convenient access to REVLIMID.

REVLIMID(R) is a registered trademark of Celgene Corporation.

RevAssist(SM) is a service mark of Celgene Corporation.

This release contains forward-looking statements which are subject to known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations expressed or implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and other factors described in the Company's filings with the Securities and Exchange Commission such as our 10K, 10Q and 8K reports.

Source: www.celgene.com

Rabbit ATG update

I have no idea what this means, but it struck me as interesting since I was the recipient of ATG as part of my chemo protocol for my allo stem cell transplant.
***
Apoptosis and complement mediated lysis of myeloma cells by polyclonal rabbit anti-thymocyte globulin

Current monoclonal antibody therapies for multiple myeloma have had limited success, perhaps due to narrow target specificity. We have previously described the ability of polyclonal rabbit anti-thymocyte globulin (rATG) to induce caspase and cathepsin mediated apoptosis in human B and plasma cells. We now extend this observation to myeloma cells. Complement in-dependent cell death was measured after addition of rATG (0.1- 1000 µg/ml) to cultures of myeloma cell lines or primary CD138+ isolates from patient bone marrow aspirates. rATG induced significant levels of apoptosis in myeloma cell as assayed by caspase induction, Annexin-V binding, subdiploid DNA fragmentation, plasma membrane permeability, and loss of mitochondrial membrane potential. Addition of complement greatly augmented myeloma cell death. Binding of rATG to individual myeloma cell surface proteins, primarily CD38, CD52, CD126 and CD138 was demonstrated by competitive inhibition experiments with targeted monoclonal anti-bodies. Three pathways of cell death were identified involving caspase activation, cathepsin D, and the genistein sensitive tyrosine kinase pathway. F(ab)₂ fragments of rATG had reduced pro-apoptotic activity, which was restored by Fc fragments, anti-CD32 or anti-CD64 antibodies. We conclude that rATG is effective agent for in vitro induction of apoptosis in multiple myeloma, and that exploratory clinical trials may be warranted.

Martin S Zand^*, Thuong Vo, Tina Pellegrin, Raymond Felgar, Jane L Liesveld, J J Ifthikharuddin, Camille N Abboud, Ignacio Sanz, and Jennifer Huggins
Division of Nephrology, University of Rochester Medical Center, Rochester, NY, USA
Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA
Department of Pathology, University of Rochester Medical Center, Rochester, NY, USA
Hematology and Oncology Unit, University of Rochester Medical Center, Rochester, NY, USA
Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA

^* Corresponding author; email: Martin_Zand@URMC.Rochester.edu

IMF expands to Europe

The International Myeloma Foundation to Establish European Base of Operations

NORTH HOLLYWOOD, CA and WÜRZBURG, GERMANY -- 12/19/2005 -- The International Myeloma Foundation (IMF) -- conducting research and providing education, advocacy, and support for myeloma patients, families, researchers, and physicians worldwide -- today announced it is restructuring its European operations. Effective mid-January, outreach to European patients, families and physicians will be coordinated through a new office being opened in Würzburg, Germany. The IMF also maintains regional headquarters in Brazil, Japan, Israel and has affiliates in Australia and Canada, with global headquarters in North Hollywood, California, USA, where the organization was founded.

"Newer, more effective and less invasive treatment regimens are becoming available for myeloma patients, and we play a crucial role in educating patients, families and physicians worldwide about the newest options and the latest medical research," said Susie Novis, founding president of the International Myeloma Foundation. "Reorganizing our operations in Europe to strengthen our presence on the Continent, dovetails with initiatives we will announce early in the New Year to strengthen our presence in Latin America and our already strong position in Israel, Australia and Japan."

The IMF has been increasingly active in Europe. Within the last five years, Patient and Family Seminars, Scientific Myeloma Symposia, and Myeloma Conferences have been held in Paris, Madrid, Barcelona, Zurich, Istanbul, St. Petersburg, Rome, Vienna, Heidelberg and Turin. In 2006, IMF activities are already slated for cities in Austria, France, Germany, Spain, Italy and the Czech Republic. A native of Germany, Gregor Brozeit, who currently is the Director of Public Advocacy for the International Myeloma Foundation, will direct the European operations.

"This restructuring will enable us to better serve the growing number of patients on the Continent and to interact directly with the dozens of local myeloma organizations being established across Europe as awareness of myeloma increases," says Mr. Brozeit. "Having spent a considerable portion of my life in both Germany and the United States, I understand the common issues and concerns patients face on both sides of the Atlantic."

The International Myeloma Foundation manages patient and physician education and outreach programs geared to the specific needs of each global region where it operates. In addition, the Foundation established and maintains Bank on a Cure®, a unique repository of myeloma genetic information with dual laboratories in the US and the UK. Recent findings reported at a major international cancer conference indicate the Bank on a Cure is helping doctors identify genetic differences that help explain susceptibility to myeloma and response to medications to help guide individualized treatment and prevention plans in the future.

ABOUT THE INTERNATIONAL MYELOMA FOUNDATION

The International Myeloma Foundation is the oldest and largest myeloma organization, reaching more than 125,000 members in 113 countries worldwide. A 501 (c) 3 non-profit organization dedicated to improving the quality of life of myeloma patients and their families, the IMF focuses in four key areas: research, education, support and advocacy. To date, the IMF has conducted more than 100 educational seminars worldwide, maintains a world-renowned hotline, and operates Bank on a Cure®, a unique gene bank to advance myeloma research. The IMF can be reached at (800) 452-CURE or www.myeloma.org.

New drug XL999

Exelixis, Inc. announced the initiation of a multi-trial Phase II clinical development program for XL999. The Phase II program is composed of six trials that will evaluate XL999 in a variety of cancer indications. Four solid tumor clinical trials are currently open for patient enrollment at several centers in the US. Two additional trials, in AML and multiple myeloma are expected to initiate in the near future. XL999, a Spectrum Selective Kinase Inhibitor(TM), is a potent small molecule inhibitor of key receptor tyrosine kinases implicated in the development and maintenance of tumor vasculature and in the proliferation of some tumor cells.

MM study of Cetuximab (Erbitux)

Blood cancer experts at the University of Cincinnati are trying to determine whether suppressing a certain growth protein can slow the progression of multiple myeloma.

Led by Dr. Rami Komrokji, the study will test the effectiveness of cetuximab (Erbitux), a targeted (monoclonal) antibody that blocks a protein on the cell surface called the epidermal growth factor receptor (EGFR). Antibodies are immune-system proteins that seek out and destroy specific bacteria and viruses.

By blocking EGFR, which helps cancer cells grow and multiply in the blood, researchers believe they may be able to slow the progression of multiple myeloma.

"This drug is different, because it attacks the ability of the cells to grow and multiply, versus killing an existing tumor," Komrokji said. "If we can slow the tumor growth, we can reduce pain and suffering associated with the disease, improving the patients' quality of life."

This is the first time cetuximab -- which is approved by the FDA to treat advanced colon cancer -- has been studied in the treatment of multiple myeloma, according to UC.

Komrokji will test the drug on about 50 patients who have previously received at least one treatment -- chemotherapy, bone marrow transplant or radiotherapy -- but show indications of disease progression.

The trial is sponsored by Bristol-Myers Squibb and ImClone.

Source: Cincinnati Business Courier

Kathy Giusti, Glamour Magazine's Hero of the Month

The Multiple Myeloma Research Foundation (MMRF) is pleased to announce that Kathy Giusti, co-founder and chief executive officer of the MMRF, has been named Glamour Magazine's "Hero of the Month." Kathy was selected for this honor for her efforts in funding innovative myeloma research and in helping to bring new, breakthrough therapies to patients as quickly as possible.

The January 2006 issue of Glamour features Kathy, along with her twin sister, MMRF co-founder Karen Andrews, in the article "Two Sisters vs. Cancer."

Source: MMRF mailing

Research into vaccine with allo stem cell transplant

Combined vaccination with idiotype-pulsed allogeneic dendritic cells and soluble protein idiotype for multiple myeloma patients relapsing after reduced-intensity conditioning allogeneic stem cell transplantation.Background and objective: To combine the use of idiotype-pulsed allogeneic dendritic cells (alloDC) and soluble protein Id conjugated with KLH (Id-KLH) in a vaccine strategy for multiple myeloma (MM).Design and methods: Four MM patients received the combined vaccine after having experienced disease relapse/progression following reduced intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) and failure to rescue therapy with donor lymphocyte infusion or chemotherapy (CHT).Results: Vaccination was well tolerated and induced an anti-KLH antibody response in all 4 patients as well as substantial cell proliferation. In contrast, no case showed similar effects against either tumor-specific Id or irrelevant isotype control immunoglobulins (Ig). In turn, vaccination was associated with modulation of biological responses linked to both inflammatory and T-cell activation, with secretion of effector Th1 cytokines. In particular, an important increase in the spontaneous ex vivo secretion of TNFalpha, IL-6 and IFNgamma as well as IL-2 and IL-10 was frequently observed prior to the fourth vaccination. Moreover, in vitro stimulation with Id-KLH and Id-KLH plus alloDC, but not with alloDC alone was associated with an enhanced number of TNF-alpha(+) T-cells and an increased secretion of IFNgamma and IL-2 before the third and fourth vaccination. From a clinical standpoint, 2 patients had a transient response and 1 has stable disease after stopping vaccination, while 3 of them ultimately progressed.Interpretation and conclusions: The results show for the first time that the use of Id-pulsed alloDC following RIC alloSCT is safe and feasible. However, crucial strategy improvements are warranted to possibly achieve clinical benefit.

Bendandi M, Rodriguez-Calvillo M, Inoges S, de Cerio AL, Perez-Simon JA, Rodriguez-Caballero A, Garcia-Montero A, Almeida J, Zabalegui N, Giraldo P, Miguel JS, Orfao A.

Laboratory of Immunology, Cell Therapy Area, University Clinic, Center for Applied Medical Research (CIMA), School of Medicine, University of Navarre, Pamplona, Spain.

A thimble of fibre

Dr. Michael Lyon, 47, takes a pass on an artery-clogging lunch buffet in favour of a nicoise salad and orders a tomato juice, which ends up being the centrepiece of his meal.

Into the juice, Lyon dumps a thimble-size scoop of a super-fibre known as PGX, invented by researchers at the University of Toronto. He stirs the juice and waits until it thickens into a tomato paste so dense a spoon can stand up in it.

He chugs it down. By the time the fibre mixture expands in his stomach he is so full he can barely finish his salad. Lyon won't be hungry again until dinner.

A little thimbleful of the fibre, called PGX -- or polyglycoplex -- contains 2.5 grams of soluble fibre, which in itself is fairly remarkable. More remarkable, it can absorb six times its weight in water, greater than any other fibre or fibre blend ever studied.

With such huge absorption power, the 2.5 grams of fibre is the equivalent of 25 grams of another popular fibre, psyllium, or 75 grams of oat bran. You'd have to eat 15 bowls of oat bran in one sitting to get the same amount of fibre.

Lyon was combing through the medical literature when he noticed a discovery by the Risk Factor Modification Centre at St. Michael's Hospital, part of the University of Toronto.

This group had discovered that soluble fibre could regulate blood sugar, lower cholesterol and control appetite. The group wanted to develop a fibre with the greatest amount of water-absorbing potential in the smallest amount of fibre.

PGX is a blend that contains the ground-up tuber root of the amorphophalus konjac c. koch plant, used as a food and remedy for thousands of years in the Far East.

When the researchers combined konjac flour with other viscous ingredients they came up with their super-fibre.

The fibre can be stirred into a shake as a meal replacement, taken as capsules, sprinkled on food or stirred into soups or tomato juice. As a once-a-day meal replacement, it costs about $100 a month.

PGX was introduced last year at the American Diabetes Association's annual scientific meeting and hailed in the media as part of the search for dieters' Holy Grail.

Clinical trials involving hundreds of patients have shown that if taken daily, PGX can greatly reduce appetite, eliminate hypoglycemic cravings and promote efficient fat burning by diminishing insulin resistance, lowering insulin levels and normalizing appetite-regulating hormones.

The large volume of food creates a sense of fullness in the stomach and results in the release of the signalling hormone CCK, which alerts the brain that the person should stop eating.

In a recent study conducted in the Vancouver area, Lyon counselled 200 chronically obese people in sensible eating and exercise, and then encouraged them to take PGX twice a day.

"Almost everyone immediately noticed their cravings went away," he says. The average weight loss was one pound a week over 12 weeks, while dozens of obese people lost more than two pounds a week.

Lyon also has great hopes for obese people who have Type 2 diabetes or have developed insulin resistance. According to current Canadian food guidelines, healthy adults should consume at least 26 grams of fibre -- ideally 26 to 35 grams -- daily. But the present Canadian fibre intake only averages 4.5 to 11 grams a day.

Lyon says fibre is the missing ingredient in many people's diets. Some African tribes consume 100 grams of fibre a day and only 1,000 calories and have almost no cancers or other major health problems.

© The Edmonton Journal 2005

Gene therapy progress: Senesco

Senesco Technologies, Inc. today announced results from the Company's funded research agreement at Mayo Clinic. Using human multiple myeloma cells grown in vitro, the data show that the Company's proprietary Factor 5A gene technology causes these cancer cells to die, thereby leaving fewer viable cancer cells in comparison to untreated samples.

Multiple myeloma is a type of bone marrow cancer that produces high levels of inflammatory cytokines which can lead to bone lesions and tumor progression. In this study, human multiple myeloma cells were grown in the presence of IL-6, a cytokine that acts as a growth factor for the myeloma cells. The aim of the study was to show that Senesco's technology could induce these dividing myeloma cells to die. Approximately 90% of the cancer cells treated with Factor 5A died, in comparison to approximately 25% of the untreated cells.

Richard Dondero, Vice President of Research and Development at Senesco, commented, "This early-stage study has shown that Factor 5A is not only able to kill myeloma cells, but also eliminate myeloma cells in the presence of IL-6. This latter finding is of interest in that it has proven to be very difficult to induce apoptosis in myeloma cells in the presence of IL-6 with standard therapies such as dexamethasone."

Based on these in vitro results, the Company and Mayo Clinic plan to determine the efficacy of Factor 5A in a multiple myeloma animal model. The animal model is an important next step in determining Factor 5A's potential ability to affect this disease.

Source: www.senesco.com

New drug Noscapine

Cougar Biotechnology, Inc., a privately held biotechnology company, today announced the presentation of results from preclinical experiments that demonstrate the effectiveness of the Company's drug CB3304 (noscapine) for the treatment of non-Hodgkin's lymphoma and multiple myeloma. The data was presented as a poster presentation at the American Society of Hematology Annual Meeting.

The preclinical studies demonstrate that noscapine exhibits potent antitumor activity against non-Hodgkin's lymphoma and myeloma in vitro as well as in vivo in xenograft models. In vivo studies demonstrated that in xenograft models, daily administration of noscapine resulted in tumor growth delays of between 30-80% of the control tumor volumes.

Owen O'Connor, MD, PhD, from Memorial Sloan Kettering Cancer Center stated "Noscapine exhibited marked activity in non-Hodgkin's lymphoma and multiple myeloma cell lines that appears to complement the activity of conventional cytotoxic therapies. As noscapine may represent a new, well-tolerated, oral therapy for the treatment of lymphoma and myeloma, further clinical studies with the drug are warranted."

New drug Aplidin

Zeltia SA unit PharmaMar SA said further investigation of its Aplidin drug in the treatment of multiple myeloma is 'warranted,' given the risk benefit profile of the drug.

In a press release relating to the Phase II results of Aplidin in patients with advanced multiple myeloma at the American Society of Hematology in Atlanta, Georgia, PharmaMar said the findings 'confirm the potential role of Aplidin as a single agent therapy in this indication.'

NIH Launches Cancer Genome Project

Genetic Mapping Could Revolutionize Treatment and Prevention, Health Officials Say

Federal health officials yesterday launched the biggest genetic research endeavor since the landmark human genome project: an ambitious effort to categorize all of the hundreds of molecular glitches that turn normal healthy cells into cancers.

The Cancer Genome Atlas, whose total cost could reach $1 billion or more, will for the first time direct the full force of today's sophisticated genetic technologies to the thorough understanding of a single disease -- one that will eventually strike nearly half of all Americans alive.

Leaders of the National Institutes of Health, which will administer the project through grants and contracts, predicted it would revolutionize the diagnosis, treatment and prevention of cancer, which will kill 564,000 Americans this year.

"This is really the beginning of a new era," NIH Director Elias A. Zerhouni said at a news conference in Washington, flanked by researchers, doctors and patient advocates.

Although the lofty rhetoric echoed that of Richard Nixon's now-disparaged call for a war on cancer almost 35 years ago, Zerhouni and others emphasized that scientists have learned crucial lessons totally unknown at that time. Most centrally, it is now known that cancer is a genetic disease, caused by errors in a cell's DNA that can be identified and targeted with molecular medicines.

By identifying the full spectrum of genetic errors that allow cancer cells to divide recklessly, spread and take root throughout the body, doctors hope to be able to classify every cancer -- not by today's crude measures of where it forms and how fast it is growing, but according to hidden molecular hallmarks that can tell which drugs will work and which ones will not.

"The planets have aligned to tackle cancer in a comprehensive way that we've never had the tools to do before," said Francis S. Collins, director of the NIH's National Human Genome Research Institute. That institute and the National Cancer Institute will provide $100 million for a three-year pilot project to test the project's feasibility.

A genetic map of everything that makes a cancer cell cancerous could speed the development of drugs that specifically target tumor cells' Achilles' heel. It could also lead to molecular imaging tools able to detect tumors when they are young, and provide clues about how to prevent them in the first place.

"The future will look no more like the past than a butterfly resembles a caterpillar," said NCI Director Andrew von Eschenbach, adding that he sees cancer devolving soon from a killer to a "chronic, manageable condition."

The Cancer Genome Atlas is the outgrowth of a year and a half of planning by NIH advisory groups. It would build on the emerging recognition that cancer is a collection of diseases that have rampant overgrowth in common but disparate genetic roots.

Some cancers are caused by a mutation in a single gene that normally keeps a cell from making offspring. Others are caused by the mistaken duplication of a gene that promotes normal cell division, boosting its reproductive capacity to abnormal levels.

In other cases, entire pieces of chromosomes -- long, gene-bearing strands of DNA inside cells -- break off and reattach to other chromosomes, inducing spurious and unregulated growth signals.

Still other cancers result when rogue molecules attach themselves to genes whose job is to control cell division. Such "epigenetic" changes are invisible on standard tests that look for mutated genes because the genes themselves are healthy but are being manhandled by the other molecules.

The Cancer Genome Atlas faces formidable challenges, not least of which will be collecting hundreds or thousands of tumor specimens -- each of which must be properly preserved, freely donated for research by patients who have been informed of the project's goals and accompanied by detailed clinical information such as the tumor's response to various drugs.

Then will come the tedious work of analyzing all the relevant genetic traits of those cells and correlating those details to the cancer's clinical characteristics. Collins likened that undertaking to "thousands of human genome projects," a reference to the $2 billion effort, completed in 2003, to learn the order of all 3 billion letters of genetic code that go into making and maintaining a human being.

Collins emphasized that gene research costs have dropped considerably in recent years and expressed hope that an initial "back-of-the-envelope" estimate of $1.5 billion for the cancer atlas will prove high.

As the atlas gets filled, its contents are to be placed on a computer database freely accessible to researchers, doctors, patients and the public.

Not everyone supports the effort. In letters to scientific journals and in other venues, some scientists have complained that now is not the time for such an effort, given the already pinched federal research budget. Others have suggested that the approach is bound to fail on scientific grounds.

Garth Anderson, a cancer geneticist at Roswell Park Cancer Institute in Buffalo, said that because cancers are by definition genetically unstable, even a single tumor has cells with different mutations, many of which played no role in its emergence. And while a few new molecularly targeted drugs have worked against cancers where other drugs have failed, he said, even those drugs typically buy patients just a few months before the tumor finds a way around the medicine.

"If it's going to cost me $100,000 to add 45 days of life, I'd rather drop dead and give my kids the money," said Anderson, who added that he puts more faith in better tumor imaging and old-fashioned surgery.

But Bruce Stillman, president of the Cold Spring Harbor Laboratory in New York and one of several experts who advised NCI on the proposal, disagreed.

"It would be ridiculous to say at this time, 'Okay, we finished the genome. Let's not do anything with it.' To say we shouldn't be doing this is to say we're not interested in solving cancer."

© 2005 The Washington Post Company

Source: http://www.washingtonpost.com/wp-dyn/content/article/2005/12/13/AR2005121301667.html

ASH: Thalidomide benefit to elderly patients

Pharmion Corporation (Nasdaq: PHRM) reported today on data abstracts from studies investigating the role of thalidomide as a treatment option for all stages of multiple myeloma. Results of these and numerous other thalidomide studies were presented at the American Society of Hematology Annual Meeting (December 10-13, 2005).

An analysis of data from a multi-center trial of 255 patients comparing the efficacy and toxicity of the combination of oral melphalan and prednisone (MP) to MP plus thalidomide (MPT) in newly diagnosed multiple myeloma (MM) patients older than 65 years of age was presented. Patients treated with MPT experienced overall response rates of 76 percent vs. 48 percent for MP alone, and near- complete response rates of 28 percent vs. 7 percent, respectively. MPT patients also had better outcomes with regard to median progression-free survival (33 months vs. 14 months), and two-year survival rates (82 percent vs. 65 percent). Looking at only those patients who completed the assigned six cycles in both study arms, the two-year survival rate was 90 percent for the MPT arm vs. 71 percent for patients given MP, a statistically significant difference. Grade III/IV adverse events were reported in 49 percent of MPT-treated patients vs. 25 percent of those treated with MP; they included thromboembolism, infections and peripheral neuropathy.

Data from a second multiple myeloma study in newly-diagnosed elderly patients demonstrated differences in overall survival, response to treatment and progression-free survival (PFS). Patients aged 65-75 were given either MPT, MP or autologous stem cell transplantation (MEL100). The study compared MPT vs. MP, MP vs. MEL100, and MPT vs. MEL100. Analysis of data from 436 patients, 191, 124 and 121 in MP, MPT and MEL100 groups, respectively, showed that following a median follow-up time of 32.2 months, the PFS time was significantly longer in the MPT as compared to the MP patient group (27.6 months for MPT and 17.1 for MP. No significant difference was seen between the MP and MEL100 groups. Based on the superior results for the MPT arm, enrollment was stopped after this analysis. The investigators conclude, based on this data, that the reference treatment for newly diagnosed multiple myeloma patients, ineligible for high-dose therapy, should be MPT.

Study Assesses Thalidomide Combination Therapy in Newly Diagnosed Patients (abstract 782)

An interim analysis of response rates from a study of previously-untreated elderly patients with multiple myeloma was presented in an oral session on Tuesday, December 13. A total of 125 evaluable patients, randomized to receive either thalidomide-dexamethasone (TD) or melphalan-prednisone (MP), demonstrated a overall response rate (ORR) of 67 percent for the TD arm vs. 48 percent on MP. Analysis per protocol revealed an ORR of 89 percent in the TD arm and 66 percent in the MP group. Data from these patients demonstrate a significantly shorter time to response and time to best response in the TD group as compared to the MP group (8 and 11 weeks for TD vs. 10 and 39 weeks for MP). Grade III/IV thrombocytopenia was more frequent and leucopenia was more statistically significantly more common in the MP group.

Data Highlight Results from Total Therapy 2 Trial in First Line MM Patients (abstract 423)

Data from a prospective, randomized study of 668 patients were presented in an oral session on Monday, December 12. This study examined the impact of adding thalidomide (T) to melphalan (MEL200)-based tandem autotransplants for multiple myeloma. While the addition of thalidomide did not significantly extend overall survival, potentially due to an imbalance of cytogenetic changes between the two arms, it did significantly increase complete response rates (41 percent with MEL200 alone vs. 59 percent with MEL200 plus T). In addition, patients receiving thalidomide with MEL200 demonstrated improved five-year event-free survival rates (42 percent for MEL200 vs. 54 percent for MEL200 plus T).

Data Assess Impact of Thalidomide Maintenance Therapy Following Autologous Transplantation in Multiple Myeloma (abstract 1148; poster session 306-I)

Interim data from 593 patients (under age 65) in a study assessing the role of thalidomide maintenance therapy among multiple myeloma patients receiving high-dose chemotherapy and autologous stem cell transplant were presented in a poster session on Saturday, December 10. In the study, designed to examine duration of response after high-dose VAD therapy, patients received two autologous transplants (with melphalan doses of 140mg/m2 and 200mg/m2, respectively); those without progressive disease after two months were randomized to receive no maintenance (arm A), pamidronate maintenance (arm B), or pamidronate maintenance with thalidomide (arm C). At the time of this analysis, the four-year overall survival was similar for the three treatment groups; however, the data also demonstrate that the four-year post-diagnosis probability of event-free survival was 39 percent for patients in arm A, 37 percent in arm B and 50 percent for arm C. The benefit was particularly pronounced among patients with a beta-2-microglobulin >2.5mg/l without deletion of chromosome 13.

"Following a single or double autologous transplant, nearly all multiple myeloma patients ultimately relapse," said Pr Michel Attal, MD, lead investigator, Service d'Hematologie, Hopital Purpan, Toulouse, France. "This study demonstrates that the addition of thalidomide to this therapy may help manage residual disease and reduce the frequency of relapse."

Source: http://www.pharmion.com

ASH: AMD3100

AnorMED announces the first report of clinical results on MOZOBIL (AMD3100), a first in class stem cell mobilizer, from the compassionate use protocol (CUP) in cancer patients requiring a stem cell transplant. Cancer patients enrolled in the MOZOBIL CUP program failed prior attempts to collect stem cells for transplant using standard mobilization regimens. Data reported shows that remobilization with MOZOBIL and G-CSF allowed patients to collect enough stem cells for a transplant. Preliminary results on the first 70 CUP patients were released today in an oral presentation given by Dr. Joseph McGuirk, Medical Director of the Kansas City Blood and Marrow Transplant Program, at the American Society of Hematology (ASH) conference.

"Stem cell mobilization is an important but difficult process for cancer patients. Depending on the type of disease, more than 20 percent of patients just can't mobilize enough stem cells, that later will get them through the intense chemotherapy they need to survive. The strongest predictor of success in transplantation is the number of stem cells available for transplantation," said Dr. McGuirk. He added, "MOZOBIL gave the patients in the compassionate use program a fighting chance to collect enough stem cells for a potentially life-saving transplant after prior attempts using G-CSF alone or chemotherapy plus G-CSF mobilization failed."

Overall 42/70 CUP patients (60%) collected the minimum number of stem cells required to go onto transplant (2 million CD34+stem cells/kg of patient weight), without having to pool prior collections, when re-mobilized with MOZOBIL and G-CSF. The median collection for the 42 patients was 4.6 million CD34+ stem cells/kg of patient weight. Of the 42 patients, 38 were transplanted, 3 expired prior to platelet engraftment due to disease progression and 30 are now at six months post transplant or beyond.

MOZOBIL & Allogeneic Transplant

Additionally, Dr. Steven Devine, Associate Professor of Medicine, Director, Blood and Marrow Transplant Program, Ohio State University School of Medicine reported an update on a pilot study from Washington University using MOZOBIL as a single agent to mobilize stems cells in healthy donors for an allogeneic transplant. Results to date show eight of nine donors collected adequate stem cells to support an allograft. The six transplanted patients have all experienced successful engraftment and have had a median follow up period of 200 days.

Note: Certain of the statements contained in this press release contain forward-looking statements which involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of the Company, or industry results, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. The Company does not expect to update any forward-looking statements as conditions change. Investors are referred to the discussion of the risk factors associated with the Company's business contained in the Company's Final Short Form Prospectus dated December 1, 2005 and filed with Canadian securities regulatory authorities and available on SEDAR.

Background on MOZOBIL

MOZOBIL has orphan drug status in both the U.S and the E.U. In December 2004, AnorMED completed the Special Protocol Assessment process with the U.S. FDA and agreed on the design and endpoints of two pivotal Phase III studies. These studies are ongoing in major transplant centers in the U.S. One study is enrolling 300 non-Hodgkin's lymphoma (NHL) patients and the other study 300 multiple myeloma patients. Both studies are randomized, double-blind, placebo controlled, comparative trials of MOZOBIL plus G-CSF versus placebo plus G-CSF.

MOZOBIL is an inhibitor of the CXCR4 chemokine receptor. The CXCR4 receptor is present on white blood cells and among other functions, has been shown to play a key regulatory role in the trafficking and homing of human CD34+ stem cells in the bone marrow. MOZOBIL is the first in a new class of agents which induces rapid mobilization of stem cells from the bone marrow into the peripheral blood system.

Source: www.anormed.com

ASH: KOS-953

Kosan Biosciences Incorporated today reported interim results from two clinical trials of KOS-953, Kosan’s proprietary formulation of the Hsp90 inhibitor 17-AAG, in two oral presentations at the 47th Annual Meeting of the American Society of Hematology. Data from a Phase I single-agent clinical trial and a Phase Ib combination trial of KOS-953 co-administered with bortezomib (Velcade®) demonstrated early signs of anticancer activity and tolerability in patients with relapsed-refractory multiple myeloma.

KOS-953 is a novel formulation of 17-AAG, an Hsp90 inhibitor. In vitro and in vivo studies showed that inhibition of Hsp90 by KOS-953 leads to protein degradation and apoptosis of multiple myeloma cells. By blocking Hsp90 function, KOS-953 markedly enhances the sensitivity of multiple myeloma cells to bortezomib (Mitsiades et al 2005, Blood Epub 18 October 2005).

Source: www.kosan.com

ASH: PXD101

CuraGen Corporation and TopoTarget A/S announced today that Phase I data on PXD101, a small molecule histone deacetylase (HDAC) inhibitor for the treatment of advanced hematologic and solid cancers, were presented at the American Society of Hematology Annual Meeting. Preliminary results on 16 patients show that PXD101 is well-tolerated following intravenous administration and has demonstrated potential anti-tumor activity against multiple myeloma, non-Hodgkin's lymphoma and transformed chronic lymphocytic leukemia.

Source: www.curagen.com

ASH: HuMax-CD38 effective in preclinical studies

Genmab A/S (CSE: GEN - News) announced today that HuMax®-CD38 was effective in killing primary multiple myeloma cells and plasma cell leukemia cells in preclinical studies. HuMax-CD38 is a human IgG1k antibody that targets the CD38 molecule which is highly expressed on the surface of multiple myeloma tumor cells.

ASH: ZymoGenetics presents TACI-ig data

ZymoGenetics, Inc. (Nasdaq: ZGEN - News) announced that preliminary data were presented from a Phase 1 study of TACI-Ig in patients with multiple myeloma and Waldenstrom's macroglobulinemia. Based on nine patients enrolled to date, study authors observed that treatment with TACI-Ig reduced circulating polyclonal immunoglobulin levels and had an acceptable tolerability profile with few treatment-related adverse events in these patients. This presentation and one discussing preclinical use of Interleukin 21 (IL-21) with Rituxan® were given at the American Society of Hematology annual meeting.

IMF DNA bank identifies genetic variations

The IMF today announced that researchers are reporting individual genetic differences that may be associated with risk factors for developing myeloma and with adverse reactions to therapies in patients who have myeloma. The findings were made with resources from Bank on a Cure®, the world's first repository of myeloma-patient DNA collected globally through large clinical trial groups, clinical centers, hospitals, and individual patients. The data were reported at the 47th Annual Meeting of the American Society of Hematology.

The findings presented at ASH demonstrate that differences in predisposition to myeloma and its treatments may be traced to single nucleotide polymorphisms or SNPs ("snips"), changes in a single letter in the DNA code of a gene. For example, the higher incidence of myeloma among African Americans may be related to SNPs that increase production of interleukin 6, or alter cell regulation. Some SNPs may also indicate the potential for neuropathy, nausea, bone pain and other toxic reactions to combination chemotherapy, while other SNPs indicate risk for blood clots associated with other therapies. In all, seven genetic variants that may influence myeloma risk and response were identified with significant differences seen among ethnic populations.

"We are expanding on these initial findings through the development of a custom panel of 3,500 SNPs that will enable simultaneous analysis of a larger number of factors than was possible until now, and we have begun testing this custom 'gene chip'," said Gareth Morgan, M.D., of the Royal Marsden Hospital in London, co-director of the Bank and co-author of Bank on a Cure presentations at ASH. "As we develop this custom SNP analysis, we will be able to move closer to the goal of personalized medicine, where finally we can better tailor treatments to individual patient needs."

The data from Bank on a Cure also showed unexpected findings. For example, although TNF-alpha, a protein associated with inflammation is elevated in myeloma patients, it may actually delay onset of the disease because of its role in other immunological processes.

"What this says to us is factors affecting myeloma are likely to be of the result of complex interactions of multiple genetic factors that are associated with risk and adverse response to treatments," said Brian Van Ness, Ph.D. of the University of Minnesota, co-director of the Bank and co-author of Bank on a Cure presentations at ASH. "Bank on a Cure has been invaluable in providing the large numbers of samples required for these studies, along with equipment and analytical tools, and the Bank's unique resources will be even more important as we use the new custom chip to look at larger numbers of genetic variations that are likely responsible for the development of myeloma and the outcome of treatment."

More than 3,000 DNA samples have been collected so far from myeloma patients in groups that have been treated with conventional medications, high dose therapies or with the novel medications. The samples along with the custom gene chip analyzers and other high tech equipment are housed at the University of Minnesota under the direction of Dr. Van Ness, and at the Institute of Cancer Research in London under the direction of Dr. Morgan. The International Myeloma Foundation expects the number of samples collected to double in the next two years.

DNA samples are stored anonymously and patient information is kept at a third, separate location to maintain confidentiality of the individuals who contribute samples to the Bank.

$1 billion for cancer research

The government of Alberta announced $1 billion in funding for cancer facilities in Calgary and Edmonton, with a goal of establishing Alberta as a world leader in research and treatment of the disease.

Premier Klein said an investment in cancer research could have payoffs for Albertans and the world.

Cancer is set to replace heart disease as the leading cause of death in Canada within five years. Nearly 38 per cent of women and 44 per cent of men in Canada are expected to develop cancer in their lives.

Harvey Weingarten, president of the University of Calgary, characterized the proposed facility as a giant leap ahead in treatment, prevention and helping those stricken with the disease.

"What is being talked about here is world-class stuff, some of the most advanced cancer research facilities in Canada, if not the world," said Weingarten.

Researchers will approach cancer from every different angle, said Weingarten.

"It runs the gamut, everything from hard-core molecular biology, to the most innovative treatment protocols, to psychological and social issues to help people deal with the disease," he said.

Election promises

Canadian Conservative Leader Stephen Harper announced that, if elected, a new Conservative government would fully implement the five-year Canadian Strategy for Cancer Control at a cost of about $50 million per year.

ASH: Velcade outperforms Dex

Millennium Pharmaceuticals, Inc. today announced extended survival data from the multi-center phase III APEX trial, the largest randomized study in relapsed myeloma, and the only trial to demonstrate a survival advantage for a single agent, VELCADE, in this setting. The results demonstrate a six-month survival advantage for patients in the VELCADE arm.

VELCADE demonstrated a median overall survival of 30 months.

The updated results, based on median follow-up of 22 months, from the APEX study continue to show VELCADE is superior to high-dose dexamethasone in overall survival and one-year survival rates, response rates and time to progression. The APEX trial was conducted at 93 centers in North America, Europe and Israel and enrolled 669 patients with multiple myeloma who had received one to three prior therapies.

Data from 669 evaluable patients showed:

• Median overall survival was 30 months in the VELCADE arm versus 24 months in the dexamethasone arm providing a six-month survival advantage in the VELCADE arm
• One-year survival was 80 percent in the VELCADE arm versus 67 percent in the dexamethasone arm
• Importantly, statistical significance was maintained even though 62 percent of patients crossed over to receive VELCADE after experiencing progressive disease on the dexamethasone arm

Data from 333 evaluable patients in the VELCADE arm showed:

• Overall response rate was 43 percent
  - 16 percent had complete (nine percent) or near-complete (seven percent) response
  - 34 percent had partial response
• Responding patients received a median number of 10 cycles of treatment
• In patients with 100 percent reduction of M-protein (measurement of disease), duration of response was longer (11.5 months)
• Although median time to response remained rapid at 1.4 months, maximum reduction of M-protein occurred in later cycles of therapy, approximately:
  - 20 percent of patients achieved best M-protein response after cycle 8
  - 30 percent of patients achieved best M-protein response after cycle 6
  - 50 percent of patients achieved best M-protein response after cycle 4
  
  Source: http://www.mlnm.com

ASH: Revlimid plus Dex better than Dex alone

Celgene Corporation announced updated clinical data from two Phase III studies evaluating REVLIMID (lenalidomide) plus dexamethasone in previously treated multiple myeloma patients. The updated clinical data from the pivotal International Phase III trial (MM-010), demonstrated that the combination of REVLIMID plus dexamethasone led to a statistically significant improvement in median time to disease progression. The updated clinical data from the pivotal North American Phase III trial (MM-009), reported that the combination of REVLIMID plus dexamethasone led to a statistically significant improvement in overall survival in addition to a statistically significant improvement in median time to disease progression. As of June 2005, median overall survival in patients treated with REVLIMID plus dexamethasone has not been reached as compared to 104 weeks with dexamethasone plus placebo.

The data were presented at the plenary session during the 47th American Society of Hematology (ASH) Meeting in Atlanta, on Sunday, December 11. Data from the International study reported that:

• The median time-to-disease progression with REVLIMID plus dexamethasone was 49 weeks, compared with 20 weeks for placebo plus dexamethasone
• Best response rate with REVLIMID plus dexamethasone was 59 percent, compared with 24 percent for placebo plus dexamethasone
• Complete response and near complete response rate with REVLIMID plus dexamethasone was 17 percent, compared with 4 percent for placebo plus dexamethasone
• Side effects were well characterized and manageable; the combination of REVLIMID and dexamethasone appeared to be well tolerated with constipation, diarrhea and neutropenia being most common.

Consistent with previous interim findings, results showed best response rates of 59% in patients treated with REVLIMID plus dexamethasone, compared to 24% of patients treated with placebo plus dexamethasone.

Patients in both REVLIMID trials had been heavily treated prior to enrollment, many having failed three or more rounds of therapy with other agents. In addition, more than 50 percent of patients in the study had undergone stem cell transplantation.

In both trials, patients treated with REVLIMID and dexamethasone had an increase in side effects as compared to patients treated with placebo plus dexamethasone. Grade 3/4 toxicities included neutropenia, thrombocytopenia and anemia. Deep vein thrombosis occurred in 4.5 percent and 13.5 percent of patients treated with REVLIMID plus dexamethasone, compared to 5.0 percent and 3.5 percent of patients treated with placebo plus dexamethasone in the International and North American trials, respectively. Pulmonary embolism occurred in 4.0 percent and 2.9 percent of patients treated with REVLIMID plus dexamethasone, compared to 1.1 percent and 0.6 percent of patients treated with placebo plus dexamethasone in the International and North American trials, respectively.

Source: www.celgene.com

CNN: Myeloma vaccine trial

'A vaccine helped cure my cancer'
By Denise Villani for CNN

(CNN) -- Denise Villani was told she had a cancer that could not be cured, but three and a half years on, after taking part in a clinical trial for a vaccine, she is cancer-free. This is her story:
More than three and a half years ago, I was diagnosed with multiple myeloma, an incurable cancer of the plasma cells. I was 47 at the time.

Plasma cells usually make up less than five percent of cells in the body's bone marrow, but if you have multiple myeloma, a group of abnormal plasma cells (myeloma cells) multiply, raising the percentage of plasma cells to more than 10 percent of the cells in your bone marrow. The result can be erosion of the bones. The disease also interferes with the function of your bone marrow and immune system, which can lead to anemia and infection, and can cause problems with kidneys.

The standard treatment is three months of chemotherapy, followed by a bone marrow or stem cell transplant. The average life expectancy after this treatment is two to five years. I had no noticeable symptoms, apart from anemia, and although the cancer had not yet affected my bones, it was a devastating scenario. I was a single mom with two sons, aged 16 and 18.

My doctors were in touch with doctors at Johns Hopkins University Hospital in Baltimore and presented me with the option of participating in a clinical trial where they would take my cancer cells and develop a vaccine. I would still receive the standard treatment, followed by the vaccine. The doctors hoped the vaccine would create an immune response within my body to resist returning myeloma cells.

I returned to hospital the week after my diagnosis, and received a four days of chemotherapy, around the clock. I did this once a month, for three months.

The aim of the chemo treatments was to lower the cancer cell count to make my body more receptive to a successful bone marrow transplant. After the third month, my body had developed a "rejection clone," which resisted the chemo. I was put on Thalidomide, an oral type of chemo that my body responded well to, and which is commonly used for chemo-resistant patients with myeloma. During these months of treatment, I was extremely fatigued. This was caused by the steroids that are often given in conjunction with certain chemo drugs. And yes, my hair fell out.

During these months, I was also visiting Johns Hopkins Hospital on a regular basis. There I had all types of tests, including bone marrow biopsies, and it was recommended I have a stem cell transplant versus a bone marrow transplant.

The death rate is quite high with a bone marrow transplant because of the risk of rejection disease, called graft versus host disease or GVH. Prior to the transplant, they took my blood and isolated, cleaned and froze the stem cells.

The week before the transplant I was given high doses of chemotherapy and whole body radiation to kill as many remaining cancer cells as possible. The transplant, similar to a transfusion, was successful and I was on the road to recovery.

I developed a pretty mean rash that was diagnosed as GVH, which should not have happened because the stem cells I'd received were my own. The doctors weren't sure how this happened, but one thought was that the vaccine (one dose was administered before stem cell collection, and pre-transplant) may have caused this when given the stem cells during transplantation.

Regardless, my doctors felt this may be the cure for me on its own, because the only enemy left to reject in my body were returning myeloma cells. The rash cleared up and after three weeks in the hospital, I was sent home to recover.

The vaccine clinical trial continued with one round of vaccines given every three weeks for eight rounds. My body continued to show signs of recovery and immune response. Any remaining cells were dwindling. By July 2003, it was written in my record, "no evidence of disease." I could only thank God and the wonderful doctors and nurses.

I have been cancer-free for more than two years. There is no evidence in my body of this "incurable" disease. I continue to live my life to the fullest every day, as I have been able to get my sons in college and continue to work full time. There are wonderful researchers doing amazing things in the field of cancer. Hopefully within a few years these procedures will be approved for standard treatment. Never give up hope.

Strontium as a bone supplement

Strontium is a nutrient from the same mineral family as calcium and magnesium that is being heralded as an effective substances for the prevention and treatment of osteoporosis.

A French pharmaceutical company named Servier has created strontium ranelate. Servier has conducted studies of the drug which show increased bone mineral density and reduced risk of fracture.

Servier's study results involving 1,649 postmenopausal women with severe osteoporosis were recently published in the New England Journal of Medicine and revealed a significant reduction in vertebral compression fractures in women treated with strontium ranelate.

However, not everyone is jumping on the strontium ranelate bandwagon. Some experts point out that Strontium is a heavy mineral which is taken up in newly forming bone and contributes to the absorption of X-rays used to calculate bone density -- and this can account for some of the observed increases in bone mineral density.

Natural health advocates are convinced that natural forms of the mineral can yield results similar to those using the synthetic ranelate form. A variety of natural heath supplement forms of Strontium are available, such as “Strontium Support”.

Guidelines and warnings for supplementing your diet with strontium:

• Strontium is not a replacement for calcium or vitamin D -- in fact all the studies utilized these in addition to strontium.
• Strontium works best when you add 1500 mg of calcium and 800 IU vitamin D to your supplement regime.
• Strontium should NOT be taken with meals or with calcium. It's best taken on an empty stomach.
• How much do you need? Recent trials have used 680 mg of "elemental strontium." Read labels carefully to establish how much elemental strontium your supplement is providing.
• Check with a physician before taking Strontium.

Japanese trial of Gamma-delta T cell therapy

Medinet has signed a joint research agreement with two medical institutions, the Japanese Red Cross Medical Center and the Shin-Yokohama Medical Clinic.

The three partners will jointly undertake through March 2006 clinical studies of lymphokine-activated killer cell therapy using gamma-delta T cells. Specifically, they aim to verify the safety and validity of cell therapy in treating multiple myeloma.

ASH: Treanda (bendamustine)

ASH platform presentations provide the latest data from company-sponsored Phase 2 multi-center registration studies on two Cephalon Oncology investigational compounds, TREANDA(R) (bendamustine HCL) and CEP-701 (lestaurtinib).

TREANDA is a novel alkylating-benzimidazole hybrid cytotoxic in which a molecular ring common to traditional alkylators is altered. Preclinical research provides evidence that TREANDA induces efficient and durable cell damage.

Bendamustine has been available in Germany for more than three decades for several indications, including NHL, chronic lymphocytic leukemia, multiple myeloma, and several solid tumors.

Source: www.cephalon.com

KRX-0401 (Perifosine) update at ASH

Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) today announced that Dr. Hideshima, of the Dana-Farber Cancer Institute, will report the results of preclinical experiments that demonstrate the effectiveness of KRX-0401 (perifosine) against multiple myeloma (MM) cells at the upcoming ASH Annual Meeting.

KRX-0401, is a novel, oral, anticancer agent that modulates Akt and several other important signal transduction pathways, including MAP kinase and JNK. KRX-0401 is in-licensed by Keryx from Aeterna Zentaris, Inc. (TSX: AEZ - Nasdaq: AEZS).

KRX-0401, or perifosine, is the prototype of a new group of anti-cancer drugs referred to as alkylphosphocholines that block proliferation and induce the apoptosis of cancer cells. This effect is relatively specific for cancer cells compared to normal cells. The mechanism of action for these drugs is not clear. They are known to modulate signaling in a number of pathways known to function abnormally during the development of cancer. One of the pathways inhibited by the alkylphosphocholines is Akt, a pathway associated with tumor survival and growth. Akt is considered to be one of the most important cancer targets being researched today.

Perifosine and Tipifarnib increases aptosis in myeloma cell lines

Novel agents are needed to improve the outcome for patients with myeloma. We have previously shown that the combination of bortezomib and tipifarnib results in synergistic myeloma cell death. This increase in apoptosis is associated with down regulation of phosphorylated AKT, a potent anti-apoptotic signaling molecule. Therefore, agents that target AKT represent ideal compounds for further study in myeloma. Perifosine is a novel, oral bioavailable alkylphospholipid. Perifosine has displayed apoptotic and antipropliferative activity in vitro and in vivo in several human cancer models including leukemia. Perifosine exerts its actions by interfering with key intracellular pathways including AKT, MAPK, JNK, p21waf1. Our hypothesis is that targeting AKT via multiple upstream pathways will result in increased myeloma cell apoptosis. Therefore, we assessed the effects of single agent perifosine with and without tipifarnib on multiple myeloma cell lines.

Combination therapy with tipifarnib and perifosine results in less cell proliferation compared to either agent used alone in the RPMI8226 myeloma cell line. The dosages employed in these in-vitro studies are lower than those used in previously published data and are clinically achievable. The goal is to develop further effective treatment options for patients with myeloma.

Rajni Sinha, Ebenezer David, Emily Zeilter, Claire Torre, Jonathan L. Kaufman, Sagar Lonial Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA

Beneficial effects of green tea

The following will be presented as a poster session at the upcoming ASH conference.

***
A Green Tea Polyphenol, Epigallocatechin-3-Gallate, induces selective Apoptosis in multiple myeloma Cells

Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, induces dose and time dependent cell death in both IL-6-dependent and independent multiple myeloma cell lines and primary patient cells, with minimal or no effect on the growth of normal cells. The cell death is apoptotic as determined by annexin V staining and is not inhibited by IL-6. Evaluation of molecular mechanism of action by gene expression profiling indicated that EGCG had a profound effect on transcription of major regulatory genes involved in distinct pathways controlling cell growth arrest and apoptosis: Exposure of myeloma cells to EGCG induced the expression of: 1) Fas ligand, Fas, and caspase 4, the initiators and mediators of death receptor dependent apoptosis; 2) death-associated protein kinase 2, a multifunctional pro-apoptotic protein kinase; 3) P53-like proteins, p73, p63; 4) CARD10 and CARD14, positive regulators of apoptosis and NF-kappaB activation; and 5) Cyclin-dependent kinase inhibitors, p16 and p18. In a subset of these selected genes, the expression data is also confirmed with western blot analyses. We have also demonstrated that the transcript and protein levels of a metastasis associated laminin receptor 1 are significantly elevated in myeloma cell lines and patient samples compared to normal cells. RNAi mediated inhibition of laminin receptor 1, abrogated EGCG-induced apoptosis in myeloma cells thus indicating that the profound anti-cancer effect of this compound is probably mediated through this receptor. The selective expression of this receptor explains the selective activity of EGCG in multiple myeloma cells without adversely affecting normal cells.

Taken together these data confirm significant and selective anti-cancer activity of EGCG, a natural product, in MM and provides the basis for its clinical evaluation.

Masood A. Shammas, Ramesh B. Batchu, Hemanta Koley, Robert C. Bertheau, Paola Neri, Raj Goyal, Kenneth C. Anderson, Nikhil C. Munshi Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; Research and Development, VA Boston Health Care, Boston, MA, USA; Medicine, Harvard Medical School, Boston, MA, USA

Human Domain Antibody (dAb)

Domantis, the human Domain Antibody (dAb) therapeutics company, today presented data showing how dual targeting dAbs (a pair of linked dAbs in a single product, each of which binds to a different target) have been used to specifically target multiple myeloma cells, while sparing healthy cells.

Speaking at IBC's 16th International Conference on Antibody Engineering in San Diego, U.S., Domantis' Executive Vice President and CSO, Dr. Ian Tomlinson explained, "Domantis scientists have shown in a series of experiments that dual targeting dAbs which bind to two different antigens on the surface of tumor cells can preferentially bind to and kill those tumor cells while healthy cells that express only one or neither of the antigens are spared.

This is a completely novel approach to tumor targeting that dramatically enhances the potency of the targeting agent by focusing its activity on tumor cells. This cannot be achieved using conventional antibodies which bind to a single target and typically kill both cancerous and non-cancerous cells."

Since it first announced the successful creation of dual targeting dAbs in 2003, Domantis has initiated three proprietary dual targeting oncology programs, initially focused on multiple myeloma, small cell lung cancer and colorectal cancer. The first two of these programs harness the ability of dual targeting dAbs to specifically target tumor cells. Most oncology drugs on the market or in development kill a broad spectrum of cells, including both cancerous and non-cancerous cells. Even blockbuster antibody therapeutics such as Rituxan are aimed at killing all B cells, rather than just those that are malignant. By enhancing the targeting of tumor cells while sparing healthy cells Domantis hopes to develop the next generation of cancer drugs, based on the unique attributes of dAbs, that are more effective and less toxic than those currently on the market.

In addition to creating better cancer drugs, dual targeting dAbs have significant potential in the treatment of multi-factorial diseases, where a number of different disease targets are implicated. Domantis has already shown that dual targeting dAbs can bind and neutralize two completely different therapeutic targets in formats that can easily be produced in microbial or mammalian cells. The Company has created a panel of proprietary dual targeting dAbs against several different pairs of targets, including one to treat asthma that neutralizes the activities of both IL-4 and IL-13. As part of its ongoing collaboration with Abbott Laboratories, Domantis has also delivered to Abbott a dual targeting dAb directed at two inflammatory disease targets. Domantis has filed a series of patent applications covering the methods of production and compositions of dual targeting dAbs.

Source: http://www.domantis.com

Novel Therapeutic Targets for Multiple Myeloma

In vitro and in vivo models have been developed that have allowed for delineation of mechanisms of multiple myeloma (MM) cell homing to bone marrow (BM); tumor cell adhesion to extracellular matrix proteins and BM stromal cells; and cytokine-mediated growth, survival, drug resistance, and migration within the BM milieu. Delineation of the signaling cascades mediating these sequelae has identified multiple novel therapeutic targets in the tumor cell and its BM microenvironment. Importantly, novel therapies targeting the tumor cell and the BM, as well as those targeting the tumor cell or BM alone, can overcome the growth, survival, conventional drug resistance, and migration of MM cells bound to BM using both in vitro and in vivo severe combined immunodeficiency mouse models of human MM. These studies have translated rapidly from the bench to the bedside in derived clinical trials, and have already led to the United States Food and Drug Administration approval of the novel proteasome inhibitor bortezomib for treatment of relapsed/refractory MM. Novel agents will need to be combined to enhance cytotoxicity, avoid development of drug resistance, and allow for use of lower doses in combination therapies. Genomics, proteomics, and cell signaling studies have helped to identify in vivo mechanisms of sensitivity versus resistance to novel therapies, as well as aiding in the rational application of combination therapies. These studies have therefore provided the framework for a new treatment paradigm targeting the MM cell in its BM milieu to overcome drug resistance and improve patient outcome in MM.

Teru Hideshima, Dharminder Chauhan, Paul Richardson, Kenneth C. Anderson

Supported by National Institutes of Health Grants No. SPORE IP50 CA10070-01, PO-1 78378, and RO-1 CA 50947 Grants; the Doris Duke Distinguished Clinical Research Scientist Award (K.C.A.); the Multiple Myeloma Research Foundation (T.H., D.C.); and the Cure for Myeloma Research Fund (K.C.A.).

Journal of Clinical Oncology, Vol 23, No 26: pp. 6345-6350
© 2005 American Society of Clinical Oncology
DOI: 10.1200/JCO.2005.05.024

From the Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Address reprint requests to Kenneth C. Anderson, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: kenneth_anderson@dfci.harvard.edu