New drug: Pomalidomide Phase II results

From the Celgene web site:

Press Releases

Data from Pomalidomide Study in Refractory Multiple Myeloma Patients Presented at ASCO

Jun 05, 2010 -- Celgene International Sàrl (NASDAQ: CELG) today announced results of a Phase II study of pomalidomide and dexamethasone in multiple myeloma patients who have failed both lenalidomide and bortezomib. Data were presented by Dr. Martha Lacy of the Mayo Clinic.

In this current analysis of the study, patients who were refractory to both lenalidomide and bortezomib were given 2mg daily of pomalidomide on days 1-28 of each 28-day cycle and 40mg daily of oral dexamethasone on days 1, 8, 15, 22.

The overall response rate (ORR) for these patients was 54% (19/35). Fourteen percent (5/35) of patients achieved a very good partial response (VGPR), 17% achieved a partial response (PR) (6/35) and 23% achieved a minor response (MR) (8/35). Additionally, at 6-month follow-up, the progression-free survival rate was 58% (95% CI: 42-80) and the overall survival rate was 86% (95% CI 73-100). The median progression-free survival was 8 months (95% CI: NA).

The most common grade 3 or 4 hematologic adverse events were neutropenia (34% 12/35), anemia (9% 3/35) and thrombocytopenia (9% 3/35).

These data are from an investigational study of pomalidomide, which is not approved for marketing.

About Pomalidomide
Pomalidomide is an IMiDs(R) compound, a member of a proprietary group of novel immunomodulatory agents. These immunomodulatory agents, taken orally, have unique multiple mechanisms of action that involve the microenvironment of the cancer cell, not just the malignant cell itself. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications in the US, EU and other regions.

About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at www.celgene.com.

This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control. The Company's actual results, performance, or achievements could be materially different from those projected by these forward-looking statements.The factors that could cause actual results, performance, or achievements to differ from the forward-looking statements are discussed in the Company's filings with the Securities and Exchange Commission, such as the Company's Form 10-K, 10-Q and 8-K reports.Given these risks and uncertainties, you are cautioned not to place undue reliance on the forward-looking statements.

Vitamin C Inhibits Velcade

Vitamin C (ascorbic acid) significantly reduces the activity of Velcade (bortezomib) in treatment of multiple myeloma, according to a recent article published in Nature.

Preclinical studies suggest that vitamin C, which is one of the most common dietary supplements for cancer patients, increases the efficacy of cancer drugs and decreases treatment-related side effects. However, more recent studies show that vitamin C can counteract the activity of certain cancer chemotherapy agents, including Velcade, in the body.

Studies have shown that a hydroxyl group (-OH) in vitamin C directly binds to boronic acid in Velcade. This significantly reduces the affinity of Velcade for the proteasome, decreasing its destructive activity toward myeloma cells.

The article published in Nature examines how Vitamin C affects Velcade activity in mice. Dr. Paul Richardson, a physician at Dana Farber Cancer Institute and Associate Professor at Harvard Medical School, said that a study testing the effect of vitamin C on Velcade’s efficacy in myeloma patients is in the planning phase. As seen in previous studies, vitamin C significantly reduced the activity of Velcade, and the degree of inhibition was dose-dependent. In order to test whether vitamin C selectively inhibits Velcade by a direct binding between vitamin C and boronic acid, the authors of the article examined if vitamin C inhibited other classes of proteasome inhibitors. Vitamin C significantly blocked the activity of MG-262, which is also a boronic acid proteasome inhibitor, but it did not inhibit NPI-0052, lactacystin, or MG-132, which all belong to other classes of proteasome inhibitors. These results suggest that vitamin C selectively inhibits proteasome inhibitors containing boronic acid.

Based on these results, the authors of the article suggest that myeloma patients receiving therapy with proteasome inhibitors, particularly Velcade, should avoid taking vitamin C supplements at the same time as their proteasome inhibitor. Vitamin C should be specifically avoided at least 12 hours before and after Velcade treatment. Furthermore, the authors advise that all antioxidant supplements, which contain hydroxyl (-OH) groups that bind and inhibit Velcade, be avoided in patients receiving treatment with Velcade and other boronic acid proteasome inhibitors. In a follow-up conversation with Dr. Richardson, he specified that patients taking Velcade only need to avoid antioxidant supplements, not fruit juices that contain vitamin C. Additionally, he emphasized that supplements only need to be avoided on days when Velcade is taken.

New Drug Zolinza

The 2009 American Society of Hematology (ASH) meeting showcased presentations on Zolinza (vorinostat), a histone deacetylase inhibitor developed by Merck Pharmaceuticals.

Zolinza alters the way a cancer cell’s DNA creates proteins. This can slow down cell proliferation, minimize mutations in DNA and control cell death. Zolinza is being investigated in combination with Revlimid and Velcade.

Vaccine trial for Leukemia

According to today's newspaper, yet another cancer vaccine trial is in the offing.

This one is for Acute myeloid leukemia (AML), which is the most common form of Leukemia in adults. The disease returns in about half of patients following therapy ... i.e., marrow transplant and chemo.

The trial is taking place at King's College in London, England.

Cells are given two genes to identify the leukemia. This increases the immune system’s ability to attack cancer cells. The research is expected to be published in the Journal of Cancer Immunology, Immunotherapy in 2011.

Let's wish them well. If successful, this therapy will likely be investigated in other types of blood cancer.

Study leaders are Ghulam Mufti, Farzin Farzaneh and Dr. Nicola Hardwick at University College London. They have developed a virus which carries the two genes into the immune system.

New approach to Allo mismatched transplants

http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20091130/stem_091130/20091130?hub=CanadaAMV2

Immune system cells treason aids growth of Multiple Myeloma

Multiple myeloma cancer cells thwart many of the drugs used against them by causing nearby cells to turn traitor — to switch from defending the body against disease to shielding the myeloma cells from harm — Dana-Farber Cancer Institute scientists report in the October issue of Cancer Cell.

The researchers found that immune-system cells known as plasmacytoid dendritic cells (pDCs) essentially assume a new identity in the presence of myeloma — promoting the growth and survival of malignant myeloma cells, helping them fend off drugs, and depleting the overall strength of the immune system.

The discovery not only helps explain a little-understood aspect of myeloma biology, but also suggests a new angle of attack on the disease. Researchers found that compounds that alight on specific sites on pDCs restore the cells' original disease-fighting character and remove a trigger of myeloma cell growth.

"Our study found an unusually large number of pDCs in the bone marrow of multiple myeloma patients," says Dharminder Chauhan, JD, PhD, of Dana-Farber, who co-led the study with Ajita Singh, PhD.

"pDCs are known to be immune system 'effector' cells — the first responders of the body's attack on disease. But why are they present in such abundance in myeloma patients' marrow?"

The disease's ability to resist even the latest drugs has prompted scientists to look more closely at the basic biology of the disease, particularly the interactions between myeloma cells and their cellular neighbors.

In the current study, Chauhan and his colleagues zeroed in on those interactions in experiments involving laboratory-grown samples of myeloma cells and animals with the disease. They found that when pDCs latch onto myeloma cells, a mutual release of proteins affects both sets of cells.

In myeloma cells, these proteins cause a spurt of growth. In the pDCs, the effect is something like that of a police officer bribed to join a gang of hoodlums. The cells abandon their role as immune system sentinels and become the protectors of myeloma cells.

"This is the first time that immune system cells have been found to be converted to another function," says Chauhan, who is also a principal associate in medicine at Harvard Medical School. Investigators don't yet know how the conversion occurs, but they suspect the proteins cause a different set of genes to be activated within the pDCs.

Encouragingly, it appears possible to awaken errant pDCs to their proper duty. Researchers found that when compounds known as CpG ODNs (cytosine phosphate guanine oligodeoxynucleotides) attach to key receptors on the surface of pDCs, the cells resume their normal immune system function and stop spurring myeloma cell growth.

CpG ODNs are already in clinical trials for other forms of cancer, and Chauhan and his colleagues hope to begin trials of the compounds in myeloma patients soon.

Dr. Ken Anderson Myeloma Update

Don't miss Dr. Ken Anderson's Myeloma update on October 29.

https://www.rmei.com/LLSmyeloma/event.html

Information available at the Lymphoma and Leukemia society.

MMRF new web site

Check the Multiple Myeloma Reseach Foundation's new web site.

http://www.themmrf.org/

Sleep to lose weight

It's possibly the world's most effortless and effective diet is simpler than author Michael Pollen's pared-down manifesto to "Eat food. Not much. Mostly plants" and far easier to swallow than the Grapefruit Diet.

Ready?

Go to bed. Sleep for eight hours.

It sounds simple, so simple that six staff members at Glamour magazine gave it a go and, in the February edition, revealed they lost an average of four kilograms each without changing anything else — how much they exercised, or how much or what they ate.

And a compelling body of research increasingly shows that, scientifically speaking, sleep as a diet aid works.

In fact, the connection between sleep, diet, stress and Canada's burgeoning weight problem — 11.3 million obese or overweight and counting, says Statistics Canada — has become a focal point for sleep researchers internationally, more so after 2004 when scientists at Stanford University in California connected lack of sleep to the alarming rise in obesity in western countries.

In their 15-year study of 1,024 volunteers with sleep disorders, they found those getting less than four hours of sleep a night were 73 per cent more likely to be obese.

While our high-fat, high-sodium, high-everything diet certainly has much to do with our national pudginess, Dr. Helen Driver, an adjunct professor of medicine at Queen's University and president of the Canadian Sleep Society, also puts the blame on sleep-killing technology.

"Edison has a lot to answer for when he invented the light bulb, because everyone started spending less time asleep," she says. "It's a technology issue; people have computers and TVs in their bedrooms, they eat or read e-mail before they go to bed. The result is they don't get a restful sleep. But I would say that if you're sleep-deprived and you follow good sleep hygiene, you will lose weight without changing much else."

How?

A lack of sleep triggers a wave of reactions in the human body that starts with the hormones leptin, ghrelin and cortisol and ends with waking up exhausted and craving fat and carbohydrates, says Dr. Joseph De Koninck, director of the University of Ottawa's Sleep Research Laboratory.

"There is no question that the hormones that control appetite are affected by the loss of sleep," De Koninck says.

And it's worse if you eat just before bed, he adds.

"People stay up late watching TV, they're on the Internet and e-mail, they get hungry and eat something high-calorie. If you eat, your sleep is more fragmented because your body is digesting."

The lack of deep, restorative rest also causes a drop in the satiety hormone leptin, which means that even after you do eat the next day, you won't feel full.

Meanwhile, the hunger hormone ghrelin rises, setting the stage for overeating.

The third hormone cortisol is strongly related to the body's daily, or circadian, rhythm, "and it's involved with metabolic regulation," explains Driver. "So stress and lack of sleep are intertwined, too."

In fact, for the busy Glamour testers — most of them are mothers — the hardest part of the Sleep Diet was going to bed at the same time every night.

The trouble is we're just not getting enough 40 winks in the first place.

Researchers at the University of Chicago also studied the sleep patterns of 669 middle-aged adult volunteers in 2006, and found that while we may bed down an average 7.5 hours a night, women actually sleep for just 6.7 of them, while men get 6.1 hours.

"The average number of hours actually spent asleep has been reduced," says Driver."

It should be up to eight hours, but it's not and it's having a negative effect."

But by learning new sleep habits — and getting any sleep disorders addressed — "You will lose weight if you get the proper amount of sleep," says De Koninck. "Your hormones will be positively affected and you will not overeat."

Sleep diet details:
- Set your bedtime. First, calculate how much sleep you need by working out when you need to get up, and counting back 7.5 hours.

Then every day, go to bed 15 minutes earlier — most people need between 7.5 and nine hours of sleep — until you notice you're waking up refreshed and without the help of an alarm clock.

At that point, you've found the optimum number of sleep hours for you.
- Keep a sleep journal. Track when you go to bed, when you awaken, any restless periods and when you ate or exercised before retiring. Also, avoid napping during the day for more 30 minutes.

"Do not be one of those people who allows bedtime and awakening time to drift," warn researchers at the University of Maryland. "The body gets used to falling asleep at a certain time, but only if this is relatively fixed."
- Other tips: Dr. Helen Driver advises getting at least a half an hour of exercise during the day — but not within a few hours of bedtime — keeping the bedroom solely for sleep or sex and developing a pre-sleep routine that could include a bath, music or reading.

"Get into a regular routine for going to bed. Cut out caffeine in the afternoon, and don't go to bed too hungry or too full. Alcohol should be in moderation and never as a sleep aid."

© Copyright (c) Canwest News Service

FDA grants orphan drug status to Keryx

Keryx Biopharmaceuticals Inc. reported that the FDA gave its developing multiple myeloma drug KRX-0401, or Perifosine, orphan drug status.

The company said a late-stage study is expected to start by the end of 2009.

Health info too small to read

Most pamphlets containing health facts don't meet the CNIB's legibility guidelines, study finds

By Chris Zdeb, Edmonton Journal

Health pamphlets are more about looks than legibility, it seems: Most can't be read by the people they're designed for.

A new University of Alberta study found only 23 per cent of 388 leaflets collected from pharmacies and clinics in the metro Edmonton area met the legibility recommendations of the Canadian National Institute for the Blind.

Cheryl Sadowski, an associate professor in the faculty of pharmacy and pharmaceutical sciences, who did the study, suspected as much. Working at a seniors' clinic part time, she's watched printed information on subjects such as safety, and more sensitive topics such as elder abuse and erectile dysfunction, being handed out to seniors who'd take one look and say, 'Oh, I can't even read this.' Some bring in the brochures or information sheets the pharmacy gave them with their medication and admit they've never read them because the print is too small.

"This is a generation that doesn't do a lot of advocacy for themselves, doesn't complain, so when we get them at the clinic complaining, you know the problem must be really bad," Sadowski says.

"We know that starting in your 40s, people's vision changes as they get older, yet so much of the printed material made available to older adults isn't taking that into consideration."

It's an issue that's growing in importance as the population ages, says Ellie Shuster, CNIB director of regional communications. The CNIB has been advocating for larger type for years.

"We believe 12-point is sort of the minimum type size for an aging demographic. Fourteen point is the standard at the CNIB."
( The Journal uses 10-point type.)

Sadowski's study found only 33 per cent of the brochures collected by pharmacy student Adriana Chubaty were printed in at least 12-point and most were printed in smaller than 10-point.

One leaflet providing information for patients with cataracts and age-related macular degeneration used a squint-inducing six-point type size, the size used in the Edmonton and area phone book.

"In my opinion, people shrink the type to fit the amount of space they have to print on and it's cheaper to do a three-panel brochure than a four-panel brochure," Shuster says.

Brian Steeves, one of several people waiting for a downtown medical clinic to open one day last week, says he's had to use a magnifying glass to read some of the information that comes with prescription medication.

"I think the print should be read with your naked eye, never mind glasses," he says.
Lyn Zinkiew says sometimes she's had to read prescription information to her boyfriend, who finds the print too small.

"I've had some elderly people who have stopped me in stores to help them read something on over-the-counter medication bottles," Zinkiew says.

"Why can't they make the print bigger for something as important as medication?" Zinkiew says. "They should have better leaflets to hand out or a handout with bigger print that you can get at the counter when you purchase the medication."

If people can't read information easily and quickly, they may not bother and they could miss something important, such as which medications shouldn't be taken with others. Their doctor or pharmacist may have told them, but having
something written is useful to refer to in case they forget.

With hundreds of pamphlets on pharmacy racks, it's understandable that pharmaceutical companies want an eye-catching design that will make theirs stand out, Sadowski says.

"Lots of pamphlets are stylized, almost marketing-driven rather than information-focused," she explains. "But if you want to educate people about reflux, for example, you're more likely to sell your reflux drug to people that can read about it. I think most of the producers of this information haven't really thought through that the people their literature is aimed at can't read it."

There's quite a bit of research these days on health literacy. People are concerned about people who speak English as a second language, the jargon used in medical settings, but it doesn't matter if you make something health-literate if the print is too small to read or printed on a busy background," Sadowski says.

Australia has legislation that stipulates how health literature must be written, but it hasn't worked perfectly, Sadowski says. Neither she nor Chubaty thinks similar legislation is necessary in Canada at this point, but guidelines are difficult to find, and the organizations that developed them need to make them more accessible for companies publishing leaflets, they say.

If all else fails, there's always the aging boomers who, unlike their elders, are less likely to tolerate pamphlets they can't read, and demand better, Sadowski says.

The study was published in the May online edition of Age and Aging, the journal of the British Geriatric Society.

Health Canada is developing guidelines for the labelling of pharmaceutical products. It is also looking at package design and look-alike/ sound-alike health product names to help prevent confusion over medication, a department spokesperson says.

© Copyright (c) The Edmonton Journal

Myeloma Genome Sequencing

The Multiple Myeloma Research Consortium has completed the sequencing of the first multiple myeloma whole genomes, which researchers will use to identify potential targets for treatments.

The Multiple Myeloma Genomics Initiative was started by the Multiple Myeloma Research Foundation and is being conducted in collaboration with the Broad Institute of MIT and Harvard and the Translational Genomics Research Institute. The initiative is a comprehensive genomic analysis program aimed at gaining knowledge about the disease's biology in an effort to speed up the progress for treatments.

The MMRC, which has a total of 15 member institutions, has now begun analyzing data from the project, and additional genomes are being sequenced, MMRF said.

The Norwalk, Conn.-based foundation is also developing a portal to make the data from the myeloma genomics program available to researchers.

Revlimid survival statistics

Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma.

Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM.

Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.

We present a pooled update of two large, multicenter MM-009 and MM-010 placebo-controlled randomized phase III trials that included 704 patients and assessed lenalidomide plus dexamethasone versus dexamethasone plus placebo in patients with relapsed/refractory multiple myeloma (MM). Patients in both studies were randomized to receive 25 mg daily oral lenalidomide or identical placebo, plus 40 mg oral dexamethasone. In this pooled analysis, using data up to unblinding (June 2005 for MM-009 and August 2005 for MM-010), treatment with lenalidomide plus dexamethasone significantly improved overall response (60.6 vs 21.9%, P<0.001), complete response rate (15.0 vs 2.0%, P<0.001), time to progression (median of 13.4 vs 4.6 months, P<0.001) and duration of response (median of 15.8 months vs 7 months, P<0.001) compared with dexamethasone-placebo. At a median follow-up of 48 months for surviving patients, using data up to July 2008, a significant benefit in overall survival (median of 38.0 vs 31.6 months, P=0.045) was retained despite 47.6% of patients who were randomized to dexamethasone-placebo receiving lenalidomide-based treatment after disease progression or study unblinding. Low beta(2)-microglobulin and low bone marrow plasmacytosis were associated with longer survival. In conclusion, these data confirm the significant response and survival benefit with lenalidomide and dexamethasone.Leukemia advance online publication, 23 July 2009; doi:10.1038/leu.2009.147.

PMID: 19626046 [PubMed - as supplied by publisher]

New Drug Pomalidomide

Researchers involved in an international trial have reported that pomalidomide is active for the treatment of anemia associated with myelofibrosis. The details of this study appeared in an early online publication in the Journal of Clinical Oncology on August 3, 2009.

Pomalidomide is an oral analog of thalidomide with significant immunomodulatory effects. It stops the growth of blood vessels, stimulates the immune system, and may directly kill cancer cells. Pomalidomide is also an angiogenesis inhibitor. A Phase I study showed a complete remission rate of 17% in patients with relapsed or refractory myeloma with daily pomalidomide. The main side effects were deep vein thrombosis, which occurred early and late. A Phase II study used an alternate-day regimen of pomalidomide in an attempt to decrease thrombotic side effects. The alternate-day schedule appeared to eliminate thrombotic complications. The complete response rate in patients with relapsed myeloma was 10%, and a greater than 50% reduction in paraprotein was achieved in half the patients.

At ASH 2008 daily pomalidomide and low-dose dexamethasone was evaluated in 37 patients with relapsed or refractory myeloma. The overall response rate was 62%, while 24% had a very good partial response.

It appears that pomalidomide can be added to Revlimid as an active derivative of thalidomide with possibly fewer side effects.

Milatuzumab-doxorubicin conjugate testing

Immunomedics, Inc. announced that the U.S. FDA has allowed its investigational new drug application to initiate Phase I/II clinical trials of doxorubicin conjugate of milatuzumab. The company noted that this is the first antibody-drug conjugate to enter human testing for the treatment of patients with multiple myeloma.

The company said that the primary objective of the open-label, multi-center study is to evaluate the safety and tolerability of the antibody-drug conjugate in patients with recurrent or refractory multiple myeloma. Preliminary information on efficacy, pharmacokinetics, and immunogenicity will also be obtained.

Milatuzumab is a monoclonal antibody that has been designed to recognise and bind to a specific structure (called an antigen) called CD74. This is a receptor protein that is often found on the surface of multiple myeloma cells and is involved in the growth and survival of the cells. By attaching itself to the CD74 on cancer cells, milatuzumab is expected to stop their development and cause the cells to die.

Milatuzumab is being studied clinically for the treatment of multiple myeloma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. Milatuzumab is the first anti-CD74 antagonistic antibody to enter clinical trials.

New Antibiotics May Target Cancer-Causing Proteins

Scientists are closer to understanding how a recently approved class of antibiotics may work against cancer.

The drugs, called thiazole antibiotics, appear to block a cellular protein called FoxM1, one of the most over-produced proteins in cancer cells, according to researchers at the University of Illinois at Chicago College of Medicine. FoxM1 is believed to play an important role in causing cells to become cancerous and may present a promising target for future anti-cancer treatments.

The researchers also found that thiazoles may inhibit proteasomes, a molecular complex within cells that disposes of old proteins marked for destruction. Recently, a number of proteasome inhibitors have shown promise against cancer. One of these inhibitors, bortezomib (Velcade), has proven effective against a number of cancers, including myeloma and certain forms of lymphoma.

The new research, which appears in the online journal PLoS ONE, points to the possible anti-cancer use of thiazoles in the future. Study author Andrei Gartel, an associate professor of molecular genetics, said that by using thiazole antibiotics in combination with well-known proteasome inhibitors, "we may see a synergy that allows us to markedly reduce the dose of any one of these drugs and still effectively kill the cancer cells."

Multiple Myeloma Genomics Initiative Sequences Myeloma Genomes

Myeloma Research Foundation (MMRF) and Multiple Myeloma Research Consortium (MMRC) announced the MMRC Multiple Myeloma Genomics Initiative has completed the sequencing of the first multiple myeloma whole genomes. This is the first time multiple myeloma whole genomes have been sequenced and will be used to identify key targets for new treatments.

“Groundbreaking data from the MMRC Multiple Myeloma Genomics Initiative will play an important role in developing better treatment options for individuals who derive little benefit from existing therapies and may ultimately help provide multiple myeloma patients with the most appropriate treatment for his or her disease,” Louise M. Perkins, PhD, Chief Scientific Officer of the MMRF. “Furthermore, knowledge from this effort could also benefit patients with other types of cancer.”

The critical task of analyzing the data from the project, conducted in collaboration with the Broad Institute of MIT and Harvard, is now underway, and additional genomes are also being sequenced. A portal to facilitate data access is being constructed and these first complete multiple myeloma genomes will be made available to researchers everywhere within the next several months.

“Through its extraordinary generosity and vision, the MMRF is enabling the important work of whole genome sequencing for multiple myeloma, and making the data publicly accessible,” said Todd R. Golub, MD, Director of the Broad Institute’s Cancer Program and co-principal investigator of the MMRC Multiple Myeloma Genomics Initiative. “This is a remarkable beginning.”

The Multiple Myeloma Genomics Initiative is a comprehensive genomic analysis program designed to rapidly accelerate progress made against multiple myeloma by significantly improving the understanding of the biology of the disease.

Spearheaded by the MMRF and conducted in collaboration with the Broad Institute and the Translational Genomics Research Institute (TGen), the Multiple Myeloma Genomics Initiative utilizes tissue samples from the MMRC Tissue Bank to advance cutting-edge research and discovery efforts that span the spectrum of genomic science. Data from the Initiative are placed into the public domain in near-real time via the Multiple Myeloma Genomics Portal, the world's only myeloma-specific repository of genomic data, and can be accessed at www.myelomagenomics.org.

The Multiple Myeloma Genomics Initiative has also just completed two other high resolution genomics profiling studies performed at TGen on the full Reference Collection of 250 patient's multiple myeloma tumor tissue. Jeffrey Trent, PhD, President and Scientific Director of TGen and co-principal investigator on the Multiple Myeloma Genomics Initiative, said, “The Multiple Myeloma Genomics Initiative has created an unprecedented opportunity to examine an extraordinary breadth of genomic information to pinpoint the most important genes and cellular processes driving the disease. Such a remarkable dataset exists for very few other cancers; it will no doubt pave the way toward personalized medicine for multiple myeloma patients.”

Pesticide link to MGUS

(NaturalNews) Just how dangerous are pesticides? No one knows the full answer to that question yet, but research is revealing that exposure to these toxins is clearly a bigger health risk than most people realize.

A new National Cancer Institute (NCI) study just published in Blood, the journal of the American Society of Hematology, has found for the first time that applying pesticides doubles the risk of developing an abnormal blood condition called MGUS (monoclonal gammopathy of undetermined significance). This disorder is characterized by an abnormal level of a plasma protein and requires lifelong monitoring with blood tests. The reason? MGUS can lead to the painful cancer of plasma cells in the bone marrow known as multiple myeloma.

The NCI research involved a study of 678 individuals, culled from a U.S. Agricultural Health Study of over 50,000 farmers who had worked with pesticides. The ages of the study participants ranged from 30 to 94, with an average age of 60. They all lived in either North Carolina or Iowa and were licensed to apply restricted-use pesticides. The research subjects were asked to fill out questionnaires to assess their occupational exposure to a wide range of pesticides and to document how long they had used pesticides. They also answered questions about the pesticide application methods they used, as well as whether they wore protective gear while applying the chemicals.

Information was also obtained about the participants' family history of cancer and their smoking and alcohol usage along with other basic health and medical data. If any research subject had a history of a lymphoproliferative malignancy, such as multiple myeloma or lymphoma, they were excluded from the study. Then, each year for five years the rate of cancer incidence and deaths in the research subject group were documented. At the end of the five year study, interviews were conducted to update the information about participants' occupational exposures, medical histories, and lifestyle factors.

The NCI research team took blood samples from the research subjects and evaluated them for MGUS. No MGUS cases were observed among those who were younger than 50. However, the prevalence of MGUS in those older than 50 was 6.8 percent. And when that figure was compared to a group of men from the general population in Minnesota who did not work with pesticides, the findings showed that the incidence of MGUS was extraordinarily high among those who applied pesticides. Bottom line: the pesticide group had double the risk of having MGUS, placing them at an elevated risk for myeloma.

"Previously, inconclusive evidence has linked agricultural work to an increased multiple myeloma risk. Our study is the first to show an association between pesticide exposure and an excess prevalence of MGUS," said lead author and NCI scientist Ola Landgren, MD, PhD, in a statement to the media. "This finding is particularly important given that we recently found in a large prospective cancer screening study that virtually all multiple myeloma patients experienced a MGUS state prior to developing myeloma.

"What pesticides appear to be the most dangerous? Of the chemicals studied, a significantly increased risk of MGUS was found among the people who used the insecticide dieldrin, the fumigant mixture of carbon tetrachloride and carbon disulfide, and the fungicide chlorothalonil. These pesticides increased the MGUS risk 5.6, 3.9, and 2.4 times, respectively. "As several million Americans use pesticides, it's important that the risks of developing MGUS from the use of pesticides is known," added senior study author and NCI investigator Michael Alavanja, DrPH, in the media statement.

New York Times - Considering Longer Chemotherapy

http://www.nytimes.com/2009/07/21/health/21canc.html?_r=2

A better way to harvest bone marrow

http://www.ted.com/talks/daniel_kraft_invents_a_better_way_to_harvest_bone_marrow.html

Study pinpoints novel cancer gene and biomarker

Research underscores need to combine genomics and basic biology in cancer gene hunt

Dana-Farber Cancer Institute scientists' discovery of a cancer-causing gene — the first in its family to be linked to cancer — demonstrates how the panoramic view of genomics and the close-up perspective of molecular biology are needed to determine which genes are involved in cancer and which are mere bystanders.

The findings are reported in the June 25 issue of the journal Nature.

"In the coming years, we can expect genomic studies [which chart the activity of thousands of cell genes] to generate hundreds or thousands of genetic elements of interest in cancer research," says the study's senior author, Lynda Chin, MD, of Dana-Farber.

"To narrow that group to the genes that actually drive cancer growth and metastasis, it's necessary to do functional studies, which focus on what individual genes do to turn a cell cancerous, and mechanistic studies, which examine how they turn cells cancerous and in what setting. It is a long and intensive effort that will leverage knowledge from different fields and different model systems."

In the study, Chin, lead author Kenneth Scott, PhD, of Dana-Farber, and their colleagues worked their way through a series of experiments — in yeast cells, multiple types of human cancer cells, laboratory cell cultures, and mouse models — to demonstrate that a surplus of a gene known as GOLPH3 can spur cancer cell growth in a variety of tissues.
It is the first gene associated with the Golgi complex, a tiny packaging plant that prepares proteins for their journey within and outside the cell, which has been found to play a role in cancer.

Chin's team also found that the protein made from GOLPH3 may serve as a biomarker for tumors that can be effectively treated with the chemotherapy drug rapamycin: tumors with a high level of the protein are more apt to shrink in response to the drug than those with low levels.

The study began with an observation made years ago that a section of chromosome 5p13 is often duplicated, or amplified, in cancers of the lung, ovary, breast, and prostate gland, as well as melanoma. The presence of this abnormality in so many different types of cancer led Chin and her associates to take a closer look at that stretch of chromosome to see what genes reside there.

Using a method called genomic qPCR that can pick out specific sequences of DNA, they found four genes in the amplified region, two of which, GOLPH3 and SUB1, were expressed at high levels, due to the increase in gene copy. To determine whether both, or either, of these genes are involved in cancer, they conducted "loss of function" tests, in which they lowered each gene's activity in a set of lab-grown tumor cells.

"When we 'knocked down' GOLPH3 expression [or activity] by 95 percent, it significantly inhibited the ability of these cell lines to grow in a semi-solid condition, a cancerous quality that normal cells do not typically share," Chin says. "Knocking down SUB1 to a comparable level had only a minimal effect."

Intriguing as this finding was, it was hardly enough to prove that GOLPH3 is an oncogene — a contributor to cancer when overexpressed within a cell.

Demonstrating that would require several experiments to ensure that GOLPH3 itself, and not a nearby "shadow" gene, is responsible for the effects. Next came gain-of-function studies to see whether revving up GOLPH3 activity can turn a non-cancerous cell cancerous. It did in both mouse and human cells.

"All these results enabled us to build a case that GOLPH3 is an oncogene," Chin states. But there was a problem. "This information wasn't very helpful for achieving our ultimate goal, which is the translation of our findings into a form that is clinically useful for patients."

Despite their discovery that GOLPH3 can promote cancer, researchers didn't know what the gene's role is in normal cells. "There was literally no information on what it does," Chin remarks. The only hint was that the protein it encodes — designated GOLPH3 — is found in the Golgi network.

The team's first attempt to uncover GOLPH3's role — using gene expression profiling to see how protein levels track with various cell functions — was fruitless. So the researchers ran experiments with yeast cells to see which proteins share GOLPH3's cell neighborhood and which proteins it interacts with.

One such partner was found to be VPS35, a component of a structure called the retromer complex. The complex's job is to recycle the antenna-like receptors that dot the cell surface.

From the many genetic screening tests that have been done in yeast, researchers knew that flaws in the retromer complex can cause cells to be vulnerable to rapamycin, just as excess GOLPH3 can. Rapamycin is known to interfere with a protein called TOR, whose job is to control yeast cell size. This suggested that the retromer complex in yeast is important for chemical signals sent to and from TOR.

Chin's team theorized that mammalian GOLPH3 also works with the retromer complex to control the activity of TOR in mammal cells (where it's known at mTOR). To test this idea, the investigators found that knocking down GOLPH3 reduced cell size just as rapamycin did. They followed those experiments with biochemical studies to explore how GOLPH3 affects cell size.

The team next sought to answer whether high GOLPH3 levels cause tumor cells to be more susceptible to rapamycin in animal studies.

They took two sets of human melanoma skin cancer cells — one of which had excess GOLPH3 and the other had normal levels — implanted them in animals, allowed them to grow into tumors, then treated them with rapamycin.

"In the animals where GOLPH3 was overexpressed, the cancer cells grew much faster, but the tumors were much more responsive to rapamycin," Chin notes, "suggesting the tumor-promoting effect of GOLPH3 is dependent on mTOR signaling."

Lastly, the team considered whether the same mechanism might be at work in human cancer cells. An experiment analyzing human tumor tissue for specific proteins suggested yes. The researchers found that non-small cell lung cancer cells with too many copies of the GOLPH3 gene also had abnormally high levels of mTOR activity.

"The mechanistic relationship we'd identified in the mouse system is also at work in human tumors," says Chin, who is also an associate professor at Harvard Medical School.

In addition to identifying GOLPH3 as a bona fide oncogene and an indicator of whether rapamycin is likely to be effective against specific tumors, the study points to the need to follow genomic studies with a rigorous examination of the biological purpose and operation of potential cancer genes, Chin concludes.

"Only then can we turn our intriguing discoveries in the cancer genome into something that is useful to cancer patients."

Co-authors include Omar Kabbarah, Mei-Chih Liang, PhD, Joyce Wu, Sabin Dhakal, Min Wu, PhD, Shujuan Chen, Tamar Feinberg, Joseph Huang, Hans Widlund, PhD, and Kwok-Kin Wong, MD, PhD, Dana-Farber; Elena Ivanova, PhD, Yonghong Xiao, PhD, and Alexei Protopopov, PhD, Dana-Farber and the Broad Institute of Advanced Cancer Science; David E. Fisher, MD, PhD, Massachusetts General Hospital; Valsamo Anagnostou, and David Rimm, MD, PhD,Yale University School of Medicine; Abdel Saci, PhD, Harvard Medical School.

Vegetarian Protection against Multiple Myeloma

I've asked this question in the past and have always been told that there is no scientific evidence of causality between diet and Multiple Myeloma.

***

Being a vegetarian cuts the risk of developing cancer, especially cancers of the blood, researchers reported today.
The overall benefit enjoyed by vegetarians over carnivores is a 12 per cent reduction in risk, according to Cancer Research UK.

But researchers were surprised to find that a vegetarian diet offers the most protection against cancers of theblood such as leukemia, multiple myeloma and non-Hodgkin lymphoma.

Vegetarians were 45 per cent less likely than meat-eaters to develop these cancers.

The study involved more than 61,000 people studied over a period of 12 years. During that time some 3,350 developed cancer.

The findings are published today in the British Journal of Cancer.

Experts said they were "surprised" at the massive protection against blood cancers enjoyed by vegetarians.

Sara Hiom, of Cancer Research UK, said: "The relatively low number of vegetarians who developed cancer in this study supports Cancer Research UK's advice that people should eat a healthy, balanced diet high in fibre, fruit and vegetables and low in saturated fat, salt and red and processed meat.

"It's understandable that there's a link between what you eat and cancers of the digestive system. But we are surprised to see an association between leukaemia, non-Hodgkin lymphoma and multiple myeloma."

Researcher Professor Tim Key, of Oxford University, said: "In particular vegetarians were much less likely to develop cancers of the blood which include leukaemia and non-Hodgkin lymphoma. More research is needed to substantiate these results and to look for reasons for the differences."

Myeloma Canada Annual Conference

Myeloma Canada’s fifth annual Patient, Family & Healthcare Professionals Conference will be held in Calgary on
September 11 & 12 at the Delta Bow Valley Hotel.

LIVING WITH MYELOMA:
Advancing knowledge and wellness through education and empowerment

The year’s Conference, hosted by the Southern Alberta Multiple Myeloma Support Group in co-operation with the International Myeloma Foundation, brings together leading researchers, clinicians and healthcare professionals who will address various aspects of living with myeloma.

The sessions will address the changing approaches to myeloma treatment, the complex decisions that must be made before recommending a treatment and the promising developments that are on the horizon.

Presentations will also be made on how to better cope with unwanted side effects, how to understand your bloodwork and how to manage your lab data.

All of this learning will empower you to help you better manage your myeloma, to have a sense of greater control and, we hope, an improved quality of life.

This year’s panel of experts and topics include:

Brian Durie, MD; Cedars Sinai Cancer Centre, Los Angeles, CA
• Philosophy of “Chronic vs. Cure”: How it Impacts Outcomes
• Myeloma Therapy: Future Directions

Nizar Bahlis, MD; Tom Baker Cancer Centre, Calgary, AB
• Myeloma 101: An Introduction

Donna Reece, MD; Princess Margaret Hospital, Toronto, ON
• Understanding Your Bloodwork
• Current Approaches to Relapsed and Refractory Disease

Morie Gertz, MD; Mayo Clinic, Rochester, MN
• Current Approaches to the Newly-Diagnosed Patient

Arthur Bradwell, MD; University of Birmingham, Birmingham, UK
• Clinical Importance of Serum Free Light Chain Analysis in Myeloma

Teresa Miceli, RN, BSN; Mayo Clinic, Rochester, MN
• Management of Side Effects

Linda Watson, RN, MN, CON (c); Tom Baker Cancer Centre, Calgary, AB
• Living When There Is No Cure

Shane Sinclair, PhD (c); Tom Baker Cancer Centre, Calgary, AB
• Beyond the Blood Counts: Finding Meaning Within a Diagnosis of Myeloma

Additional speakers will address quality of life issues and break out sessions will provide the opportunity to attend presentations of specific interest.

For those attending Friday’s session, there will be a reception and dinner on Friday evening. This will provide attendees with the opportunity to meet and network with other conference participants and medical experts.
REGISTER BEFORE JULY 31 TO TAKE ADVANTAGE OF THE SPECIAL EARLY BIRD REGISTRATION FEE

For full agenda details and online registration, go to the Myeloma Canada website www.myelomacanada.ca and click on 2009 Conference.
http://www.myelomacanada.ca/en/2009_conference.htm

Secure credit card payments can be conveniently made online using PayPal.

To register by mail, please download the registration form from the Myeloma Canada site and mail the completed registration form, along with cheque payable to Myeloma Canada and mail to:

Myeloma Canada Conference Registration
5640 Lodge Crescent SW
Calgary, AB
T3E 5Y7

To register by fax, completed registration forms can be faxed to:
(403) 242-1100

Attendees wishing to stay overnight can take advantage of the special Myeloma Canada room rate of $149.00 at the Delta Bow Valley Hotel.
http://www.deltabowvalley.com/gfamcb911


Myeloma Canada / Myélome Canada
Uniquely devoted to Canada's myeloma community
Exclusivement au service de la communauté canadienne du myélome

Mailing Address/Adresse postale:
PO Box / CP 326
Kirkland, QC
H9H 0A4

(514) 570-9769
Email/Courriel: info@myelomacanada.ca
Web: www.myelomacanada.ca

Ottawa seizing Mexican Thalidomide

First the medical isotope fiasco, now this!?

Canadian patients 'starting to die,' drug firm says

Cancer patients desperate enough to order cheaper, unlicensed versions of the drug thalidomide from Mexico now face another challenge to getting treatment: Federal authorities have reportedly begun seizing supplies of the life-extending medicine at the border.

"Health Canada is stopping every single box of thalidomide," said an official with a Mexican company that makes the pills, who asked not to be named. "Patients are starting to die because of this."

Patient advocates said they had also heard reports that Health Canada and the Canada Border Services Agency have instituted a crackdown on shipments of thalidomide from Mexico and other developing countries.

Health Canada officials would not comment directly on whether they had stepped up seizures, but said their policy has always been to bar unsanctioned imports of such drugs into the country.

The development has nevertheless heightened calls on provincial governments to reimburse the steep costs of the one permitted brand of thalidomide and a similar, newer drug, both of which can add years to the lives of people with multiple myeloma, a rare blood cancer.

Some Ontario patients are even thinking of moving to British Columbia, the one province that covers the newer medicine, said Lori Borsos, a myeloma sufferer in Hamilton.

"If you need this drug to stay alive and you can't afford it, what's your choice?: move to B. C. or move six feet under," she said.

"We all live in Canada and some of us have better health care than others. It's not right."

Thalidomide -- infamous as a morning-sickness remedy that caused widespread birth defects in the 1950s and 1960s -- has proven to be one of the most effective myeloma treatments, but its cost is not officially picked up by any province.

Revlimid, a new drug that acts in a similar way and can cost $100,000 a year, is covered only in British Columbia. Velcade, the other medication widely used by myeloma patients, is financed to at least some extent by most provinces, but is not suitable for all patients.

Private insurance and manufacturers provide some funding, too.

The "core" issue is that provincial governments should pay for all three drugs, said John Lemieux, president of the Myeloma Canada support group. "The patients ... are the sole victims" of the current patchwork of funding policies, he said.

The North American-patented version of thalidomide, made by Celgene Corp. of New Jersey, can cost $40,000 a year, though the firm says it provides it free to about 60% of patients prescribed the medicine. Myeloma Canada says it has been unable to confirm that figure.

Regardless, the rest must either pay out of their own pockets, go without and face shortened lifespans or order versions made in Mexico, Brazil or elsewhere in the developing world.

The cost of one Mexican brand is about one-twentieth of Celgene's. The firm says approximately 100 Canadians have bought thalidomide from it, while other patients have sought supplies from as far afield as India.

Days after a National Post article revealed patients were importing the medicine from overseas, however, Canadian authorities began seizing Mexican shipments of the drug, the pharmaceutical company official said.

Mr. Lemieux said in an e-mailed response that his group has heard reports of as many as 20 patients having their shipments seized, but could not confirm them.

"If they don't have this drug, they will die," said the Mexican company official of her customers.

Some doctors have warned that patients risk consuming substandard product if they order thalidomide from such manufacturers, whichcurrently face no scrutiny from regulators here. Others physicians, though, say the Mexican drug seems to be just as effective and safe as the Celgene product, called Thalomid.

Thalomid is not licensed in Canada, but can be legally ordered by doctors under Health Canada's special-access program, designed to make treatments not yet approved here available on an emergency basis.

It was allowed under the program partly because Celgene, the manufacturer, has an extensive program for dealing with the drug's infamous side effects, Health Canada said in an e-mailed statement. Celgene only provides a month's supply at a time, and requires doctors to submit negative pregnancy tests for female patients of child-bearing age before dispensing more pills, the regulator said.

"Health Canada believes that this care and caution is both necessary and appropriate and is commensurate with the risks associated with the drug," the statement said.

A request for the Mexican thalidomide was made under the special-access program a few years ago, but its maker had no such program in place, the department said.

Source: http://www.nationalpost.com/news/story.html?id=1696051

Proteolix Clinical Data from Two Clinical Studies of Carfilzomib in Multiple Myeloma

Proteolix, Inc. announced data from ongoing Phase 2 and Phase 1b clinical trials of carfilzomib for the treatment of multiple myeloma at the 14th Congress of the European Hematology Association (EHA) in Berlin, Germany. Carfilzomib is the first in a new class of selective, irreversible proteasome inhibitors being developed by Proteolix for the treatment of hematologic malignancies and solid tumors.

Relapsed Multiple Myeloma Patients Achieve Responses with Single-Agent Carfilzomib

Keith Stewart, M.B., Ch.B., Professor, Division of Hematology/Oncology at the Mayo Clinic, Arizona presented positive data from an ongoing Phase 2 clinical trial of single-agent carfilzomib in relapsed multiple myeloma patients. Patients in the study have relapsed after receiving one to three prior therapies and are stratified according to prior exposure to bortezomib.

A total of 31 patients have been enrolled in the Phase 2 clinical trial to date, of which 45 percent had no prior bortezomib experience and 55 percent relapsed following bortezomib treatment. In both arms, substantial response rates were achieved and sustained. Bortezomib-naive patients achieved an overall response rate of 57 percent with a median duration of response of 8.5 months. The median time to progression in this cohort has not been reached.

Among patients with prior bortezomib exposure, 18 percent achieved partial responses and the median duration of response has not yet been reached in this population. The median time to progression for patients in this cohort was 8.9 months. Ten additional patients achieved stable disease.

"Carfilzomib monotherapy achieves durable responses in relapsed multiple myeloma patients regardless of their prior exposure to bortezomib, and notably, a number of patients remain progression free after twelve cycles," said Dr. Stewart. "Further, carfilzomib has been generally well tolerated, and the compound's selectivity appears to avoid the off-target effects, such as peripheral neuropathy, associated with currently available proteasome inhibitors."

Adverse events were generally mild and manageable and carfilzomib has been well tolerated for up to one year. Of 31 patients treated, 29 percent have received 12 full cycles of treatment.

These data were reported by Dr. Stewart in an oral presentation, titled "# 0474: Safety and Efficacy Update of PX-171-004, an Open-label Phase II Trial of Carfilzomib in Relapsed Multiple Myeloma," on Saturday, June 6, 2009.

Carfilzomib Combination with Lenalidomide is Well-Tolerated; Achieves Responses in Heavily Pre-treated Patients at Low Doses

Positive preliminary data from an ongoing Phase 1b dose-escalating trial of carfilzomib in combination with lenalidomide
and low-dose dexamethasone in relapsed and refractory patients was presented by Michael Wang, M.D., of the University of Texas MD Anderson Cancer Center on Sunday, June 7, 2009. The Phase 1b clinical trial is designed to evaluate safety and to establish a maximum-tolerated dose of carfilzomib in combination with lenalidomide and dexamethasone administered on a 28-day treatment cycle. Lenalidomide in combination with dexamethasone is currently indicated for use in patients with multiple myeloma who have had at least one prior therapy.

To date, the combination of carfilzomib and lenalidomide was well tolerated in heavily pre-treated patients and adverse events were manageable. The most common adverse events reported include anemia and fatigue. No cases of peripheral neuropathy, a common adverse event associated with approved proteasome inhibitors, have been reported. A maximum-tolerated dose has not yet been established and dose-escalation in this trial continues.

Sixty-one percent of the 18 patients evaluable for efficacy achieved very good partial, partial or minor responses. Responses occurred in the first 28-day cycle of treatment at doses well below the maximum-tolerated dose for either lenalidomide or carfilzomib alone. Initial responses improved with continued therapy. Potent inhibition of the proteasome has been observed and the lenalidomide/dexamethasone combination does not appear to interfere with carfilzomib's activity.

"Results observed to date in our Phase 1b combination study of carfilzomib are very promising," said Michael Kauffman, M.D., Ph.D., Chief Medical Officer of Proteolix. "We believe that carfilzomib in combination with lenalidomide and dexamethasone should provide superior activity to lenalidomide and dexamethasone alone. In addition, the lack of overlapping toxicities and absence of peripheral neuropathy may allow for long-term dosing - and ultimately, sustained clinical benefit."

Dr. Wang presented interim data from the Phase 1b clinical trial during the Novel Therapeutics and Drug Resistance session in an oral talk, titled "#1070: PX-171-006: Phase IB Multicenter Dose Escalation Study of Carfilzomib (CFZ) plus Lenalidomide (LEN) and Low Dose Dexamethasone (LODEX) in Relapsed and Refractory Multiple Myeloma (MM) - Preliminary Results."

About Carfilzomib

Carfilzomib is the first in a new class of selective, irreversible proteasome inhibitors. Carfilzomib produces specific and sustained inhibition of the proteasome, leading to apoptosis in cancer cells with minimal off-target effects. In Phase 1 and Phase 2 clinical trials, carfilzomib has demonstrated single-agent activity in hematologic malignancies and solid tumors, including multiple myeloma, Waldenstrom's macroglobulinemia, mantle cell lymphoma and renal cell carcinoma.

Proteolix is conducting a comprehensive clinical development program evaluating carfilzomib for the treatment of multiple myeloma, including an ongoing accelerated approval study in heavily pre-treated relapsed/refractory patients and a Phase 2 clinical trial in relapsed patients stratified by prior treatment with bortezomib. Both Phase 2 clinical trials are being conducted by Proteolix in collaboration with the Multiple Myeloma Research Consortium (MMRC). A Phase Ib clinical trial of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma is also ongoing. In addition, Proteolix is conducting a single-agent Phase 2 clinical trial of carfilzomib in patients with recurrent or advanced solid tumors. For the latest information regarding ongoing carfilzomib clinical trials, please visit www.clinicaltrials.gov.

About Proteolix

Founded in December 2003, Proteolix, Inc. is a privately-held biotechnology company, headquartered in South San Francisco, dedicated to discovering, developing and commercializing novel therapeutics that target protein degradation pathways for cancer and autoimmune diseases. Proteolix's lead product, carfilzomib, is the first in a new class of selective, irreversible proteasome inhibitors. Proteolix is also developing a pipeline of novel proteasome inhibitors, including a selective, oral proteasome inhibitor and a selective immunoproteasome inhibitor. For additional information on Proteolix, please visit www.proteolix.com.

Revlamid Presentations at the 14th Congress of the European Hematology Association

Celgene announced that data from multiple studies presented at the 14th Congress of the European Society of Hematology demonstrate that REVLIMID provides powerful and sustained responses in patients with multiple myeloma. These key presentations support the advantage of active long-term disease control along with manageable safety profiles, leading to unprecedented survival times.

"Together, the studies presented at this congress demonstrate that the use of REVLIMID early on in the course of the disease allows for rapid and durable responses that lead to the best survival benefits we've seen yet for this patient population," said Jean-Pierre Bizzari, Senior Vice President and Group Head of Global Oncology/Hematology for Celgene. "We are excited that the dual mode of action of REVLIMID, which includes both a direct killing effect against myeloma cells and a unique immune-enhancing effect, controls and manages the disease over the long-term."

Speed of response with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma: First results of the MM-019 German compassionate use protocol

Treatment time required for patients with multiple myeloma to respond to therapy with REVLIMID plus dexamethasone was examined in a phase IIIb, open-label, non-comparative trial. Patients had received at least one previous therapy and were treated in 28-day courses that were repeated until disease progression, toxicity or withdrawal by the physician or patient.
Patients' previous therapies, including transplantations, bortezomib and thalidomide, did not influence response rates. Fifteen patients (12%) had been previously treated with all three regimens, 43 (35%) with two and 42 (34%) with one.
Best response information, measured by levels of M protein and free light chains (FLC), was available for 113 patients, including four patients with a complete response, 80 with a partial response, 28 with stable disease and one with disease progression.

Time to a 50 percent reduction in M-protein or FLC was analysed for 122 patients. For responding patients, median time to response was 28 days, with 39 percent of patients seeing a response in two weeks.

"These data demonstrate that nearly three-quarters of patients achieved a partial response or better, despite having been heavily pretreated," said Dr. Katja Weisel of University Hospital in Tubingen, Germany. "The responses were rapid, with half of the patients responding well within the first treatment course."

Longer duration of treatment and maintenance of best response with lenalidomide plus dexamethasone increases overall survival (OS) in patients with relapsed/refractory multiple myeloma

A subset analysis of updated, pooled data from the MM-009/MM-010 international phase III trials demonstrated a survival benefit upon continued treatment with REVLIMID(R) plus dexamethasone after achieving best clinical response in patients with relapsed or refractory multiple myeloma.

Survival estimates for patients achieving a partial response or better were compared between patients on continuous treatment (those still undergoing treatment or who discontinued due to disease progression) and patients who discontinued treatment early due to adverse events, consent withdrawal or other reasons. Median follow-up time for surviving patients was 48 months.

The estimated median survival time for patients continuing treatment after achieving a partial response or better (N=174) was 50.9 months [95% confidence interval: 43.0-NR], while the median survival time for those who discontinued treatment early (N=38) was 34.95 months [26.4-55.7; P=0.0594].

When differences in the groups' patient characteristics (such as age, number of prior treatments, etc.) were also taken into account, the group that continued treatment had significantly better survival outcomes than did the group that discontinued therapy.

The number of patients who discontinued early due to adverse events was low (N=22, 10%).

"This study suggests that therapy with REVLIMID plus dexamethasone should be prolonged even after the patient achieves an initial response," concluded Dr. Jesus San Miguel of the University Hospital of Salamanca in Salamanca, Spain. "The lasting effects gained by additional rounds of treatment may significantly prolong survival for these patients."

Lenalidomide-based therapy leads to improvement in humoral immune system in relapsed or refractory multiple myeloma patients who respond to the therapy

Dr. Rachid Baz of the Moffitt Cancer Center & Research Institute, in Tampa, FL, USA presented another analysis of MM-009/MM-010, as well as of a large phase II study of REVLIMID(R) as a single agent therapy in patients with relapsed or refractory multiple myeloma, demonstrated that REVLIMID therapy improves patient immunity by boosting immunoglobulin A (IgA) levels.

Levels of IgA, an important antibody for fighting infections, are commonly reduced in patients with multiple myeloma. These low levels are associated with recurrent bacterial infections - the most common cause of death for patients in advanced stages of the disease.

The study measured baseline levels of the antibodies and evaluated antibody responses to therapy on a monthly basis. Improvement was defined as an increase in antibody levels to at least the lower limit of normal and a 25 percent increase in value.

Only patients who responded to therapy showed significant improvement and normalisation of residual IgA levels. At baseline, residual IgA levels were normal in 30 and 17 percent of responders in MM-009/MM-010 and MM-014, respectively. With treatment, normalised IgA levels were found in 56 percent of responders in MM-009/MM-010 by cycle seven and in 50 percent of responders in MM-014 by cycle five.

Patients whose IgA levels normalised had significantly longer progression-free (29-77 weeks) and overall (121-220 weeks) survival times compared to those whose IgA levels did not improve (P=0.0001).

Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma

Also of note is a study that was recently published in the European Journal of Hematology. This subset analysis of MM-009/MM-010 demonstrated the benefit of initiating REVLIMID plus dexamethasone at first relapse compared to later salvage therapy.

The study showed that, with REVLIMID plus dexamethasone, patients who had received one prior therapy demonstrated significant improvements compared to those who had received two or more prior therapies in outcomes such as median time to disease progression (17.1 vs. 10.6 months; P=0.026), median progression-free survival (14.2 vs. 9.5 months; P=0.047), complete or very good partial responses (39.8% vs. 27.7%; P=0.025) and median overall survival (42.0 vs. 35.8 months; P=0.041).

"These results suggest that it may be beneficial to patients to be treated with REVLIMID plus dexamethasone earlier on in the treatment course," said Dr. Edward A. Staudtmauer of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. "Based on the findings, the combination of REVLIMID and dexamethasone should be considered as a second-line therapy for patients with multiple myeloma."

REVLIMID is approved in the United States, the European Union, Canada, Argentina, Peru, Bolivia, Columbia, Guatemala, Switzerland, Malaysia, Israel, Singapore and Russia in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy and in Australia and New Zealand in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy.

Prunes Promote Bone and Heart Health

Better Heart and Bones with This Sweet Snack

Looking to satisfy your candy cravings with something tasty and good for you? Try a handful of nature’s guilt-free treats: dried plums. Research shows that they promote both heart and bone health.

Buff Bones

A laboratory study of the polyphenols in prunes showed that they boosted bone formation, density, and strength. How? By affecting the way certain bone-regulating gene cells are expressed.

A Plum Choice for Your Heart

Results from animal studies suggest that dried plums can help keep arteries clear. Researchers suspect that prune flavonoids help reduce the inflammation that plays a big role in artery disease.

Big Benefits, Little Package

If that isn’t enough motivation to pick up a pack of prunes, consider this: Just 10 prunes delivers 20 percent of your daily potassium and copper requirements, 14 percent of your iron requirements, and 10 percent of your manganese and zinc requirements. Prunes also provide a whopping dose of the essential vitamins A, C, E, and B-complex, including folate. And we all know that prunes are a super source of fiber.

Do prunes conjure up a vision of your grandma saying something about regularity? Meet today’s marketing replacement the dried plum! Full of antioxidants, dried plums (okay . . . prunes) are a delicious and sweet treat.

Source: http://www.realage.com/ct/eat-smart/food-and-nutrition/tip/8787

Combination bortezomib and doxorubicin in relapsed/refractory multiple myeloma

Shah JJ, Orlowski RZ, Thomas SK

The first in class proteasome inhibitor bortezomib (B) received its initial regulatory approval for therapy of patients with multiple myeloma (MM) in the relapsed/refractory setting. Modulation of proteasome function, however, is also a rational strategy for chemosensitization, and a variety of agents have shown synergistic activity with bortezomib pre-clinically, including anthracyclines. This formed the basis for evaluation of a regimen of bortezomib with pegylated liposomal doxorubicin (PLD).

PLD+B, in a phase I study, induced a predictable and manageable toxicity profile, and showed encouraging anti-MM activity. In a recent international, randomized phase III trial, PLD+B demonstrated a superior overall response rate and response quality compared to bortezomib alone, as well as a longer time to progression, duration of response, progression-free survival, and overall survival.

Sub-analyses revealed benefits in almost all clinically relevant subgroups, including several which would be considered to have high-risk disease. These findings have led to the establishment of the PLD+B regimen as one of the standards of care for patients with relapsed and/or refractory myeloma. Efforts are now underway to build on this combination further by adding other active anti-myeloma agents.

Down syndrome reveals key to fighting cancer

People with Down syndrome rarely get most kinds of cancer, and U.S. researchers have nailed down one reason why — they have extra copies of a gene that helps keep tumours from feeding themselves.

The findings could lead to new treatments for cancer, the researchers reported in the journal Nature on Wednesday, and further study of Down patients might reveal more ways to fight tumours.

The researchers at Harvard University and elsewhere made use of a new kind of embryonic-like stem cell called an induced pluripotent stem cell or iPS cell. These cells, made from ordinary skin, can be transformed to act like powerful stem cells, the body’s master cells.

Using iPS cells from a volunteer with Down syndrome and mice genetically engineered to have a version of the condition, the researchers pinpointed one gene that protects against tumours.

“It is, perhaps, inspiring that the Down syndrome population provides us with new insight into mechanisms that regulate cancer growth,” they wrote. Down syndrome is the most common genetic cause of mental retardation, occurring in one out of 700 live births. The Down syndrome theory had long been explored by Harvard’s Dr. Judah Folkman, who died last year. Folkman, whose name is on the study, developed theories about how tumour cells grow blood vessels to nourish themselves in a process called angiogenesis.

Folkman also noticed how rare cancer is among Down patients, except for leukemia, and he wondered whether the genes explain why. A study of nearly 18,000 Down’s patients showed they had 10 per cent the expected rate of cancer.

People with Down syndrome have a third copy of chromosome 21, where most people have two copies.
The extra copy gives them extra versions of 231 different genes.

“One such gene is Down syndrome candidate region-1 (DSCR1, also known as RCAN1),” Harvard’s Sandra Ryeom and colleagues wrote.

This gene codes for a protein that suppresses vascular endothelial growth factor or VEGF — one of the compounds necessary for angiogenesis.

Genome sequencing of multiple myeloma

The Multiple Myeloma Research Foundation (MMRF) announced a collaboration with the Broad Institute of MIT and Harvard to systematically uncover the molecular changes underlying multiple myeloma by whole genome sequencing of individual patient tumors. The MMRF will provide both patient samples for analysis as well as funding for the project. All data from this collaboration will be put in the public domain.

"We are delighted to work with the MMRF, which has been a visionary organization in accelerating cancer research for the sake of patients and their families," said Eric S. Lander, PhD, Director of the Broad Institute. "Through our work together on this critical pilot project in whole cancer genome sequencing, we hope not only to advance clinical progress for multiple myeloma, but to build knowledge and technical capabilities that can be applied to many other human cancers."

"Three years ago, the MMRF launched a partnership with the Broad Institute and the Translational Genomics Research Institute — the Multiple Myeloma Genomics Initiative — a comprehensive genome mapping program to identity new targets and eventually new therapies for this incurable disease," said Kathy Giusti, Founder and CEO of the MMRF, and a multiple myeloma patient. "As part of that larger effort, we are confident that this groundbreaking research will accelerate the development of next-generation treatments to extend the lives of multiple myeloma patients. Additionally, we believe that this work will not only ultimately pave the way to a cure for patients with multiple myeloma, but will benefit patients with other types of cancer."

The creation of comprehensive catalogs of all commonly occurring cancer mutations is a current approach of several national and international consortia, including The Cancer Genome Atlas (TCGA) led by the US National Institutes of Health and the International Cancer Genome Consortium (ICGC), to understand major tumor types such as leukemia, lung cancer, glioblastoma and others. To date, only a handful of whole cancer genomes have been sequenced and only one has been published.

"The few cancer genomes sequenced to date have been informative, but we need many more to transform cancer research and ultimately cancer therapy," said Stacey Gabriel, PhD, Co-Director of the Broad Institute's Genome Sequencing and Analysis Program. "This exciting collaboration with the MMRF will advance these goals by contributing public domain data."

Importance of Oral Hygiene

Good oral hygiene and proper dental care apply to all age groups but the needs of the elderly population can be slightly different than the needs of younger people.

I will try to list several areas of concern and how they pertain to this age group.

Why save your teeth?

A missing tooth affects many things including your oral health, your bite, your speech, your general health and your appearance.

When a tooth is lost, the remaining teeth may drift into the empty space, causing changes in biting and chewing and possibly causing pain in your jaw from the bite being misaligned. Remaining teeth may be more prone to decay if they are misaligned.

Many speech sounds that we make are made because of the position of the tongue against your teeth or the roof of your mouth. Having missing teeth can cause changes in a person's speech.

People with missing teeth often cannot chew their food properly to be digested and subsequently may end up with digestive problems and/or nutritional deficiencies.

Missing tooth will affect your appearance and may have a negative effect on one's self-esteem.

Oral health and your heart
Recent research shows that there is a link between periodontal (gum) disease and heart disease. People who have gum disease may be at a higher risk for heart attacks, although no one is certain how this happens. The current theory is that bacteria present in infected gums can become loose and move throughout the body. The same bacteria that cause gum disease and irritates our gums might travel to your arteries.

What can you do? Proper home care, including brushing and flossing regularly, is essential as well as regular visits to your dentist for periodontal maintenance.

Oral health and bisphosphonates
Patients who have been receiving intravenous bisphosphonates should avoid having teeth pulled at all costs. Many people are being treated with bisphosphonates for a variety of medical problems including osteoporosis, multiple myeloma, breast, lung and other cancers and Paget's disease. While those medications are terrific in treating a number of medical conditions, there is a risk of developing an osteonecrosis (breakdown) of the jaw bone as a result of an invasive dental procedure while taking these medications.

The most important step to prevent these problems is to have a dental consultation before beginning the bisphosphonate therapy and having all invasive procedures done before therapy is initiated.

Oral health and diabetes
It is estimated that one-third of the population in the U.S. has diabetes, yet only one-half of these patients are diagnosed.
The biggest problems for diabetics from a dental point of view are infections, periodontal disease and salivary problems.
Infections can result in improper healing following extractions and other surgical procedures.

Diabetics are very susceptible to periodontal disease and in their case it may be more severe and more difficult to maintain than in a person without diabetes.

Finally, salivary flow can be diminished in diabetics, which will result in a higher rate of caries (cavities).

Proper diet, good oral hygiene and regular dental visits can help keep the oral problems of diabetes in check.

Oral health and tobacco use
While the usage of tobacco has been declining in the last decade, it is still very high in the population and its consequence in the mouth is oral cancer. While the rate of oral cancer isn't as high as with other cancers, it is often devastating and fatal.

A word to the wise is sufficient with tobacco use, both smoking tobacco and chewing tobacco.

If you currently use tobacco, quit immediately. If you don't use it, don't start.

Older patients' dental needs
In tough economic times such as these, there is concern about the cost of maintaining one's oral health.

One doesn't need to do high-cost elective dental procedures if there are monetary constraints. But there is a need for all patients of all ages to maintain proper oral hygiene and seek regular professional care to prevent the consequences of neglect.

Keep periodontal disease under control with proper brushing and flossing techniques and regular cleanings.

Have broken teeth fixed or extracted before they result in infections.

Have ill-fitting dentures fixed or replaced so they don't cause irritations.

Have an oral cancer screening regularly.

Prevention is more prudent and less costly than repair.

Dr. Francis X. Barra, Doctor of Dental Surgery, is the director of dentistry at FoxCare Dental Associates and is a member of the medical staff at A.O. Fox Memorial Hospital in Oneonta.

Thalidomide sourcing from offshore

Owing to costs, Canadian myeloma patients are acquiring lower-cost Thalidomide from countries like Mexico, Brazil and India.

Canadians buy the drug over the Internet, in person in Mexico, or friends and relatives bring it back.

The cost is a fraction of that in Canada, athough self-importing Thalidomide is illegal in Canada.

Thalidomide costs in Canada can reach $40,000/year. Provincial drug plans and private insurers do not usually reimburse the expense.

Apparently Health Canada may permit a patient to bring up to a 90-day supply of Thalidomide into Canada.

Although Revlimid and Velcade are approved by Health Canada most provinces refuse to fund them.

A Mexican company, Laboritorios Serral, produces Thalidomide under the brand name Talizer. Apparently the drug can be imported or family members can pick up the drug from an authorized pharmacy in Mexico, if they have the patient's prescription and identification.

However, Canadian doctors are concerned about taking drugs without Health Canada oversight.