IMF Living Successfully with Multiple Myeloma

This article is right on the money. Myelomics will recognize a lot of it from first-hand experience.
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By Peter Tischler (excerpted from IMF at www.myeloma.org)

When I was diagnosed with multiple myeloma (MM) and was led to believe that I would only be around for a few years, I thought about what I wanted from medical science. I decided that I wanted quality of life and a chance to survive until a cure was found, with a reasonable quality of life during that survival. I also wanted to avoid undue pain and suffering--I'm a bit of a wimp! As I learned about our disease and how to survive with it, I was often distressed that so many people with MM had not availed themselves of their best chances of survival and quality of life. In some cases, it was not their fault. They hadn't yet had time to learn how to optimize their chances. But in other cases, both the patient and caregiver had abdicated their care to someone who is overworked and cannot possibly devote enough time and resources to them--their doctor. As good as your doctor might be, he (or she) doesn't have the time to do everything for you.

So who's going to take care of you? Who will take that responsibility? It had better be either you or someone who loves you, because nobody else will have the time, energy, resources, and desire to take on the job.

The following is a list of things that you (patient, caregiver, family) must know and do in order to best ensure that you will survive with the quality of life you want.

1. Take care of your kidneys

• Drink at least three liters of non-carbonated, non-caffeinated, non-alcoholic liquid each day in order to flush your kidneys.
• Avoid ionized contrasts that are typically used for CT scans. Ask for alternative contrast or don't let them use contrast. Failing to do this could cause your kidneys to shut down and the only solution would be dialysis. Injections for MRI and PET/CT scans are okay.
• Read labels on medications and over-the-counter products. Especially avoid non-steroidal anti-inflammatory drugs (e.g. Ibuprofen).

2. Avoid infections

• Limit exposure to people who have colds. Be mindful around children, especially during the cold/flu season. In public places (restaurants, church, etc.) stay away from children and anyone else who is coughing and/or sneezing; ask to be seated elsewhere. When flying, consider wearing a mask. Don't be so vain as to think it's ok. Your life depends on being careful.
• Develop a habit of washing your hands frequently. Always carry anti-bacterial cleaner (e.g. Purell) and anti-bacterial wipes.
• Make sure your family members get a flu shot every year. The flu shot may work for you, but it will definitely work for your family and, thereby, protect you.
• Be proactive if you do get an infection. A "simple" bronchial infection can easily become a life-threatening pneumonia in your depressed immune system.
• Wound infections easily turn into a sepsis crisis in you. If a wound is not healing properly, seek medical attention quickly.
• With your immune system, any temperature over 101 (some say 100) is cause for medical attention.

3. Form a survival team

• You (patient, caregiver, family member) have to be the head of the team. Nobody cares as much about the issues as you do. Make sure that your caregiver has as much knowledge about your condition as you do. At times of treatment with steroids and other chemo drugs you may become overwhelmed with all the information you need to keep straight. Your caregiver is your link with sanity and good judgment.
• We usually get a local oncologist by circumstance. If that oncologist doesn't meet your needs, change oncologists. Make sure it's somebody you can count on in a crisis (there usually will be crises, at some point).
• Find a myeloma specialist who can direct your treatment. That's somebody who researches and treats only myeloma. There aren't many, so don't be fooled into thinking that someone who has treated a few MM cases is a specialist.
• Have a good internal medicine physician. Hopefully, you will be in this for the long haul. You need to keep up your general health.
• If you have kidney problems, consult with a nephrologist and add him/her to your team.
• Add any other specialists for any other chronic conditions you might have.
• Don't forget nurses--they know much more about symptom control than doctors.
• Make sure that they all get copies of reports from each other. This is your team--make sure they can work together and remember that you're the team leader.

4. Don't be a "good" patient

• Make it clear, to each physician, what you (patient and caregiver) want and expect from your medical team members. They are often not all that concerned with issues (e.g., quality of life) that are important to you. You must make sure those other issues are considered by everyone.
• Get copies of your file records from all your doctors. By law, they cannot be withheld from you, and you need them in order to be team leader.
• Do not let your physicians "snow" you with medical jargon or condescend to you with overly simplistic explanations. Keep asking questions until they are communicated to your satisfaction.
• Acquire a small cassette recorder and, with the physician's permission, record all appointments. Explain that it's because you don't want to forget anything that is said. Also, take notes during the appointment.
• It's okay to say, "Let me think about that" when your oncologist tells you that "we're going to start treatment immediately," unless he means that he's going to take the drugs also. This is a very slow-growing cancer and you need to think, research, talk with others, and even get a second opinion.
• Ask for treatment options (that's plural) and the pros and cons of each one. Ask why he/she favors the one being recommended.
• When something is wrong, complain--loudly. When something hurts, complain--loudly.
• Question anything that you're not satisfied as being right, especially with technicians and office staff. But don't become a general pain in the butt. You have to pick your battles--fight and win the important ones.

5. Educate yourself (This may be you, your spouse, or a family member)

• Attend at least one IMF Patient & Family Seminar and participate in it. Go to the breakout sessions and ask questions. Spend time with other MMers there and learn how they're surviving.
• Attend a local support group as regularly as you can. There are things to learn and you need to feel "part of" a group of survivors. Even physicians can't give you what other survivors can – their experience.
• Read the "Myeloma 101" written by Peter Tischler and provided by the North Texas Myeloma Support Group. It will explain your disease in lay terms.
• You'll need a computer and connection to the Internet. The IMF website has an incredible amount of up-to-date information that is essential to the family with myeloma.
• Subscribe to the IMF's online support group of over 1,400 myeloma members worldwide. The daily experiential information is essential for anyone who wants to be proactive in his/her quest for quality survival. You might not understand much at first, but you will quickly become knowledgeable.

6. Maintain your immune system
Your immune system is defective, but it isn't dead. Optimize it with healthy habits:

• Reduce stress. This is important, as stress can further depress the immune system. Find ways to chill out and relax (in spite of it all).
• Exercise. Also important both physically and emotionally. Find ways to exercise within your limitations. Low impact is best.
• Good diet. Don't go crazy, but try to avoid stressing your systems with "bad" food choices.
• Use multi-vitamins to ensure that your systems are not deprived of any essential nutrients. You might consider a nutritionist or dietician. Those taking steroids must be especially careful.
• In some cases, an endocrinologist might be added to your team in order to ensure that you're staying in balance.

7. Keep medical records

• Trends are important. As you collect your test results, track the important markers (good and bad) so that you will see any trends developing. Learn which markers are significant and use a spreadsheet to visualize trends.Keep all your records in chronological sequence in one or more binders so that you can easily access them when needed.
• Keep shorthand medical notes in your purse or wallet: e.g. up-to-date medicine list with dosages, physicians with their phone numbers, testing schedule (even doctors will forget or get them wrong, sometimes).
• Fill out important forms for possible crisis times: Living Will, Medical Power of Attorney, and Do Not Resuscitate (DNR). It's good to have them even if you don't choose to use them.

8. Know your doctors' limitations

• Doctors and nurses are, in most cases, overworked and understaffed. That's the managed care system and you have to learn how to best work with it and get what you need.
• Doctors make mistakes; so do nurses, technicians, and office staff. That's a fact of 21^st century life and your job is to catch the mistakes. Mistakes that have happened to me include:
• Not ordering tests that should be ordered (that's why you have to keep those records)
• Wrong or inadequate instructions for imaging studies
• Not recognizing a trend (those records again)
• Miscommunication between doctor and staff
• Over-medicating and under-medicating
• Oncologists have a "treatment philosophy" they've adopted through success and failure with other patients. You may not even hear about a treatment from an oncologist because of that physician's experience with it. You may, on the other hand, be urged to take a drug or dosage that's no longer considered cutting edge or even out of common use because of that physician's past experience. You must work through that with your oncologist.
• Oncologists may be either too aggressive or too conservative to suit your needs. You must deal with that or get another oncologist.
• Some oncologists are unwilling to communicate with or take direction from other oncologists, especially myeloma specialists. Deal with that or change oncologists.
• Some oncologists are unwilling to listen to or accede to the wishes of the patient and family. Deal with that or change oncologists.
• Some oncologists are unwilling to be educated with information from you or the IMF or published studies. Definitely change oncologists.
• Know your doctors' strengths and weaknesses. Nobody, your doctor included, knows everything.

9. Early Warning System--Avoiding Crises

• Testing is used to track the disease and for tracking the success (or failure) of treatments. It's also important to you to test when on plateau so that you will get an early warning when the disease reappears.
• The most important early-warning test is the Freelite Test. This test will show disease progression before any damage occurs.
• Some tests should be run early in your journey with myeloma, even though they're not yet needed for tracking, in order to establish baseline results for tests that will be needed later in your journey. Whole-body MRI, quantitative immunoglobulins, and a bone density test could be run in addition to the usual skeletal survey with x-rays.
• Consider having prophylactic medications available, especially if you are going to travel. Consider a good antibiotic (I have Levaquin), an antiviral (I have acyclovir) and something to use for flu (I have Tamiflu).
• Avoid unnecessary surgery, as the trauma of surgery might trigger an MM "flare." If surgery is necessary, have your oncologist keep close tabs on your markers after the surgery.

Above all, react immediately when something is not right. The caregiver must make sure that the person with MM does not "tough it out." Once in a crisis, it could be too late to stop a cascade of system failures in an immune compromised person. "Toughing it out" when it comes to pain is ridiculous. Your oncologist should prescribe a pain medication that will keep you comfortable.

Myeloma: a survivor's story

One morning in 1991, as Ken Stoll was getting ready to go to work, he felt a pain in his sternum. He was 47 years old.

“It was a tightness in my chest area. It took me to my knees,” he recalled. “I thought I was having a heart attack.”

His doctor thought he may have “pulled something” and prescribed an some anti-inflammatory pills, but Stoll, an attorney who lives in North Little Rock, “still didn’t feel right.”

His doctor sent him to a hospital for tests. A few days later, Stoll got the news.

The tests showed he had multiple myeloma. “I didn’t know what that was,” Stoll said, “but it didn’t sound good.”

Stoll’s physician agreed that the diagnosis was serious. But he offered some hope.

“He said, ‘There’s a man at UAMS who just came up here from M.D. Anderson. He’s supposed to be really good.’ ”

Stoll called Barlogie’s office for an appointment. “I hung up,” he recalled, “and within 15 minutes, Dr. Barlogie called me. That was on a Friday. He said he’d made arrangements for me to come in the following Monday.”

Tests and bone-marrow biopsies confirmed the diagnosis.

“Dr. Barlogie told me they could treat me in the standard way, with just chemotherapy and drugs, and I would have in the neighborhood of maybe three years.

“He said with a bone-marrow transplant, they could maybe extend that to five years — which sounded better than three.”

Stoll’s wife was 46. His three children were in high school and college. “So,” he said, “I started the treatments.”

Barlogie put Stoll on a comprehensive regime he called “Total Therapy I.” It included chemotherapy and a bone-marrow transplant, followed by more chemotherapy.

“They get you pretty much as close to dying as you can get,” Stoll said, “and then they bring you back.”

That was in December 1991. By the following February, Stoll had gone into remission. Slowly, he was able to return part-time to his job at the U.S. Attorney’s office.

At this point, Stoll’s life-expectancy could still be measured in less than a handful of years.

“But,” Stoll explained, “Dr. Barlogie’s a believer in tandem transplants.” So a second bone-marrow transplant was conducted in April. Because his immune system had been so weakened by the treatments, Stoll was placed on the virus-fighting drug interferon.

Throughout the process, he understood the risks of Barlogie’s “high-dose treatment.”

“But,” he said, “I also understood that by not taking that risk, there wasn’t much hope at all.”

The treatment worked. Then, Stoll said, while he was in remission, “Dr. Barlogie wanted to do another collection of stem cells, in case I ever needed them in the future.”

Eventually, Stoll was able to return to work full-time and to “carry on a normal life.” By the end of last year, off of drugs completely, he had begun to see Barlogie only on an annual basis.

In his years as a patient, Stoll has seen Barlogie’s treatment regimens progress from Total Therapy I, where he began, to Total Therapy III. While he has survived, he’s known many who have not.

“I think I came through this a lot better than a lot of other patients,” he said. “I’m blessed and I’m fortunate.”

Stoll now volunteers at MIRT, working the waiting room outside the chemo section. He makes coffee and talks to patients, some of whom come to the institute for up to seven months at a time.

“I tell them I had my treatment 14 years ago,” he said. “It seems to help out a little.”

For a moment, Stoll’s eyes filled with tears as he spoke of Barlogie. “I believed in him,” Stoll said.

“He’s very personable. Most of the time, he rides a motorcycle to work. He usually comes in wearing either blue jeans or chaps from that. He hugs me. He hugs my wife.

“He’s very smart and he’s very caring, and he’s always wanting to know, ‘Did everything go okay?’ because if you had some problem some place along the line, he wants to know about it. He has a caring interest in patients — more than just a doctor in research.”

After a pause, Stoll added: “If there’s any controversy, put me on Barlogie’s side.”

Source: The Arkansas Times http://www.arktimes.com/

Vaccine clinical trial against cancer

Australian scientists believe a vaccine now undergoing its first human trials could give hope to thousands of men diagnosed with potentially deadly prostate cancer.

The vaccine, developed over the past six years by the Mater Medical Research Institute in Brisbane, helps a patient's system identify its own cancerous cells and then destroy them.

Prostate cancer affects one in 11 Australian men but the odds shorten dramatically if there is a family history of the disease, which kills more than 2500 each year.

The director of the Brisbane institute, Professor Derek Hart, said the trial used a two-step procedure involving the extraction of dendritic cells, or specialised white blood cells responsible for controlling the body's immune response.

Hart discovered dendritic cells in 1979.

But he said it could take several more years of trials before the vaccine was widely available.

"If we are successful and there is suitable development via a commercial route, it could become a routine therapy in three to five years' time."

In the meantime, 12 patients with advanced prostate cancer will be assessed over a year for the phase one trial.

The vaccine could also have applications for other cancers, Hart said.

"In a sense this is generic so we can synthesise the proteins from breast cancer, multiple myeloma, melanoma and other tumours.

"The fundamental process we are working on of manufacturing the DCs [dendritic cells] from a patient can be applied to any patient."

The study has the thumbs up from a 72-year-old Rockhampton resident, Lex Irvine, who was diagnosed with prostate cancer in 1999.

Irvine has undergone two vaccination sessions with no side effects.

"They are saying there's a very good chance it will be successful," he said.

"The alternatives I had weren't all that great."

The Brisbane institute also beat off competing medical research organisations to win $1.3 million in funding from the US Army for a similar prostate cancer vaccine, using a single-step procedure.

Clinical trials on humans are expected to begin later this year.

Bone marrow registration needed

The attached story reinforces the need for healthy people to register with a bone marrow clinic. In Canada, only 3-4% of the population donates blood regularly. The number of people who register their bone marrow is only a fraction of the population. This makes finding an unrelated bone marrow donor (or stem cell donor) a very chancy proposition.

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FOUR years ago, Mobo winner DJ Swing was touring the world with top US R'n'B artists. But in January 2003 a back pain was diagnosed as multiple myeloma.

A long wait for a bone marrow transplant ended in November, but he's appealing for potential donors to keep registering. Paul Rhys reports on a drive to save lives - given more urgency by the death of singer Lynden David Hall last week

DJ Swing is not out of the woods yet.

The Mobo award-winning artist, who pipped Fatboy Slim to the Best Club DJ title in 1998, has been given hope in his long battle against rare blood cancer multiple myeloma.

He was finally matched with a bone marrow donor last year, and is recovering at home after a successful operation.

But with the donor's bone marrow only a 90 per cent match with his own, there's still a chance he could die. Whatever happens, the 39-year-old Battersea DJ is determined that the search for suitable donors for thousands of people battling cancers and blood diseases is stepped up.

As an African Caribbean, Swing - real name Brian Daly - had only a one in 100,000 chance of finding a suitable donor.

For white people, the chance is one in five.

Worse news is that the number of black donors is woefully few. Publicity surrounding his condition - he was the subject of a Channel4 documentary, Saving DJ Swing - did ensure more people from the black community signed up to join a register of potential donors.

But campaigners are concerned that messages allaying fears about being a donor have failed to get through. And with top soul singer Lynden David Hall succumbing to the cancer Hodgkin's lymphoma on Tuesday last week, they fear people may believe the battle has been fought and lost.

Now Swing's friends - event managers Courtney Myton and Simone Ishmael, of Unlimited Entertainment - have stepped in to get the message across that more people will die if the fight does not go on. They're putting on a gig to raise cash desperately needed for donor registration clinics - and to make sure the black community knows it needs to act to save its own.

Showcase UK, at the Clapham Grand on March 19, will feature signed and unsigned UK R'n'B, soul and hip-hop artists.

There will also be 80s and new age break-dancers in homage of Swing's original DJ crew, the Boogie Bunch, and a tribute to Earlsfield's Lynden David Hall.

Mr Myton, 26, told the South London Press: "Time is of the essence. "People can help - you could be a perfect match for someone needing a transplant and in the time it takes to hesitate they could die. "By reaching out and registering, you're saving lives. "This is people's mothers and brothers, it could be your neighbour. "What happened to Lynden could happen to anybody. "Our heart goes out to his family."

Potential donors in the black community have been hard to reach.

Reasons include fears that donation is against religious teachings, that infections could be spread from needles, and that donating could be painful.

Miss Ishmael, 25, said: "People think if they come forward as a donor there'll be a big operation, that they'll have their spine opened up and marrow scraped out. "It's just a matter of a few pints of blood, a lie down and a cup of sweet tea."

Viral link to prostate cancer?

A newly identified virus, called XMRV, may be associated with prostate cancer, according to new research.

XMRV is related to a virus that causes leukemia in mice and is a "newly identified infectious agent in humans," according to Dr. Eric Klein. "While more research is needed to confirm our findings, this could be the first evidence that a virus is linked to prostate cancer," he added.

Researchers used a DNA ViroChip containing the genetic sequences of nearly 5,000 viruses to screen prostate tumor samples from 86 men. They compared the incidence of viral infection between men who had two mutated copies of HPC1 gene and men with one or no mutated copies of this gene.

Klein and colleagues found XMRV in 45 percent of the 20 men with two mutated copies of the HPC1 gene but in only 1.5 percent of the 66 other men.

The researchers are planning a comprehensive study to look at the possible association between medical histories, viral infection, and prostate cancer.

If XMRV is found to cause prostate cancer, it could be a target for drugs or a vaccine.

Thal, Dex and Zometa decreases bone resorption in myeloma patients

Background: Bone involvement is frequently observed in multiple myeloma (MM) patients both at diagnosis and during the course of the disease. The evaluation of biochemical markers of bone turnover could allow a dynamic evaluation of the effects of a given therapy on bone metabolism.

Methods: In the present study, markers of bone resorption [urinary free pyridinoline (PYD), deoxypyridinoline (DPYD), N-terminal telopeptide of collagen I (NTX) and C-terminal telopeptide (serum crosslaps)] and of bone formation [bone alkaline phosphatase (BAP) and osteocalcin] were evaluated at diagnosis and after induction therapy in 40 patients (23M, 17F, median age = 53.5 yr) enrolled in the 'Bologna 2002' clinical trial. By study design, all patients received 4 months of combined thalidomide (100 mg/d for 2 wk then 200 mg/d), dexamethasone (40 mg/d on days 1-4, 9-12, 17-20/28 on odd cycles and on days 1-4 on even cycles) and zoledronic acid (4 mg/28 d).

Results: At diagnosis, although bone resorption markers were increased in more than 40% of the patients, only NTX and crosslaps were significantly related to the extent of skeletal lesions, as assessed by X-ray. After 4 months of therapy, a significant decrease in mean urinary NTX and serum crosslaps was observed in patients obtaining partial response or greater, at variance to what has been detected in patients showing less than partial response.

Tosi P, Zamagni E, Cellini C, Parente R, Cangini D, Tacchetti P, Perrone G, Ceccolini M, Boni P, Tura S, Baccarani M, Cavo M.

Institute of Hematology and Medical Oncology 'L. e A. Seragnoli' Bologna University, Bologna, Italy.

PMID: 16480429 [PubMed - as supplied by publisher]

DVd vs. VAD

Results published in the journal Cancer show the chemotherapy agent Doxil® (pegylated liposomal doxorubicin) is preferred to Adriamycin® (doxorubicin) in VAD. Doxil reduces the risk of serious side effects to the heart while still being effective in the treatment of multiple myeloma.

VAD is a common treatment of patients with multiple myeloma (Oncovin® [vincristine], doxorubicin, and dexamethasone). However, cumulative exposure to doxorubicin can lead to serious heart problems.

A new version of Doxil has a slow release mechanism. Smaller doses are delivered, it stays in the body longer, increased concentrations of the drug accumulate in cancer cells vs. healthy cells, and side effects are reduced.

A phase III clinical trial was recently conducted in the U.S. to evaluate Doxil as a replacement for doxorubicin in the VAD regimen among MM patients. This trial included 192 patients with newly diagnosed MM who were treated with either conventional VAD or with a DVd regimen, which substitutes Doxil for doxorubicin. The DVd regimen showed responses achieved in 44.4% of patients, and 39% of patients treated with VAD. Progression-free survival was similar between the two treatment groups.

Heart complications were reduced with DVd compared to VAD. Myeloma patients planning to undergo treatment with VAD may wish to speak with their physician regarding their individual risks and benefits of treatment with DVd (note however, Doxil is not yet approved for multiple myeloma).

Reference: Rifkin RM, Gregory SA, Mohrbacher A, et al. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma.

Source: Cancer. 2006;106: 848 – 858.

Velcade results from the SUMMIT trial

BACKGROUND: Bortezomib, a first-in-class proteasome inhibitor, has shown clinical activity in relapsed, refractory multiple myeloma in a pivotal Phase II trial, SUMMIT.

METHODS: Patients received bortezomib 1.3 mg/m(2) on Days 1, 4, 8, and 11 followed by a 10-day rest period for up to 8 cycles. Dexamethasone 20 mg on the day of and the day after bortezomib was permitted for suboptimal response. Extended treatment beyond 8 cycles was offered to patients whose physicians felt they would benefit from additional therapy. Follow-up was conducted in all patients for a median of 23 months, an additional 13 months from the original report.

RESULTS: Of 202 patients enrolled in SUMMIT, 193 were evaluable for response. Seven (4%) patients achieved a complete response, 12 (6%) achieved a nearly complete response, 34 (18%) achieved a partial response, and 14 (7%) had a minimal response while on bortezomib. The updated median duration of response to bortezomib alone was 12.7 months. The median overall time to progression for all SUMMIT patients was 7 months. For responding patients, the median time to progression was 13.9 months, whereas for those with progressive disease (PD) or who were not evaluable, the median time to progression was 1.3 months. The median overall survival (OS) for all SUMMIT patients was 17.0 months. Whereas the median OS for patients with PD or who were not evaluable was 8 months, the median OS for responding patients was not reached at 23 months of follow-up.

CONCLUSIONS: These data demonstrate that treatment with bortezomib results in meaningful long-term benefit for patients with relapsed and refractory myeloma.

Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin DH, Rajkumar SV, Srkalovic G, Alsina M, Anderson KC

Department of Medical Oncology/Hematologic Malignancies, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts

Cancer 2006. (c) 2006 American Cancer Society.
PMID: 16470606 [PubMed - as supplied by publisher]

Second auto or allo transplant after first auto

BACKGROUND: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually develop a disease recurrence. However, to the authors' knowledge, the optimal salvage treatment for these patients is not well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage therapy. The outcomes of salvage autologous or allogeneic transplants were analyzed retrospectively in patients relapsing after an autograft.

METHODS: Fourteen patients (median age, 52 yrs) received a second autograft for salvage, whereas 26 patients (median age, 51 yrs) underwent a reduced-intensity allogeneic transplantation (related in 18 patients and unrelated in 8 patients). The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The two groups were evenly matched with regard to other disease characteristics.

RESULTS: After a median follow-up of 18 months for the autologous group and 30 months for the allogeneic group, the median progression-free survival (PFS) and overall survival (OS) in the 2 groups were 6.8 months versus 7.3 months and 29 months versus 13 months, respectively. Acute and chronic graft versus host disease (15%) was the most common cause of nonrecurrence mortality in the allogeneic group and infections (14%) in the autologous group. On univariate analysis, an interval of > 1 year between the first and the salvage transplant predicted a better OS in the allogeneic group.

CONCLUSIONS: Both autografting and allografting are feasible as salvage therapy for myeloma patients who develop disease recurrence after the first autograft, although disease progression remains the major cause of failure. Better approaches are needed for salvage therapy in patients developing disease recurrence after an autograft.

Qazilbash MH, Saliba R, De Lima M, Hosing C, Couriel D, Aleman A, Roden L, Champlin R, Giralt SA. Department of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston, Texas

Cancer 2006. (c) 2006 American Cancer Society. Cancer. 2006 Feb 2;
PMID: 16456814 [PubMed - as supplied by publisher]

NIH genetic initiatives

The Department of Health and Human Services (HHS) today announced the creation of two new, closely related initiatives to speed up research on the causes of common diseases such as asthma, arthritis and Alzheimer’s disease.

One initiative boosts funding at the National Institutes of Health (NIH) for a multi-institute effort to identify the genetic and environmental underpinnings of common illnesses. The other initiative launches a public-private partnership between NIH, the Foundation for the National Institutes of Health (FNIH) and major pharmaceutical and biotechnology companies, especially Pfizer Global Research & Development of New London, Conn.; and Affymetrix Inc. of Santa Clara, Calif., to accelerate genome association studies to find the genetic roots of widespread sicknesses. The genetic analysis component of the two initiatives is highly complementary.

Genes and Environment Initiative
HHS Secretary Mike Leavitt announced on Monday that the President’s budget proposal for fiscal year (FY) 2007 includes $68 million for the Genes and Environment Initiative (GEI), a research effort at NIH to combine a type of genetic analysis and environmental technology development to understand the causes of common diseases. The FY 2007 budget represents a $40 million increase above the $28 million already planned for these efforts in the NIH budget.

If approved by Congress, this additional federal funding will begin in FY 2007 and continue for multiple years. Of the first year’s funding, $26 million will go to genetic analysis and $14 million for the development of new tools to measure environmental exposures that affect health.

“The discoveries made through these efforts will ultimately lead to profound advances in disease prevention and treatment,” Secretary Leavitt said. “These are the kinds of innovative efforts that we should support. We must seize the historic opportunity provided by the Human Genome Project and the International HapMap Project, to speed up the discovery of the genetic causes of common diseases like diabetes and hypertension. At the same time, it’s critical that we also understand the environmental contributors to sickness, and the interplay among genes and environment. There is not a moment to be lost.”

GEI will have two main components: a laboratory procedure for efficiently analyzing genetic variation in groups of patients with specific illnesses and a technology development program to devise new ways of monitoring personal environmental exposures that interact with genetic variations and result in human diseases.

The proposed federal funding level will enable GEI to perform genetic analysis — or genotyping — studies for several dozen common diseases. The exact diseases to be studied will be determined by peer review. An initial survey of existing NIH-supported clinical studies identified more than 100 with sufficient numbers of already characterized patients to get this effort started. In addition, NIH expects to develop four new environmental monitoring devices a year.

“This initiative would not have been possible a year or two ago,” said Elias A. Zerhouni, M.D., Director of the National Institutes of Health, an agency within the Department of Health and Human Services. “This is a tangible result of the nation’s increased investment in medical research over the past 10 years. We are now poised to combine what we have learned from years of population studies, with newly available technologies, developed with NIH support. These technologies reduced the cost of genotyping by more than 100-fold, making such a comprehensive effort affordable. Equally important, this effort will dramatically increase our understanding of the environmental factors of health and disease, and help us develop novel measures of gene-environment interactions. We stand on the threshold of creating a future that will revolutionize the practice of medicine by allowing us to predict disease, develop more precise therapies and, ultimately, pre-empt the development of disease in the first place.”

Public-Private Partnership
At the same time, a public-private partnership between NIH, FNIH, which is a non-profit foundation established by Congress to support the mission of the NIH; Pfizer and Affymetrix is being created to further accelerate this important research on the genetic association studies.

The new partnership, called the Genetic Association Information Network (GAIN), is being launched with a $5 million donation from Pfizer to set up the management structure and $15 million worth of laboratory studies to determine the genetic contributions to five common diseases. Affymetrix, a biotech company that develops the types of tools used in these kinds of genetic studies, will contribute enough laboratory resources to study two additional common diseases. On average, it costs about $3 million to carry out one study.

“We’ve translated early information from genetic research into valuable medicines for HIV/AIDS, heart disease and the prevention of organ rejection,” said Martin Mackay, Ph.D., Senior Vice President Worldwide Research & Technology, Pfizer Research & Development. “But these advances have only scratched the surface of possible revolutionary approaches to treat and cure diseases. Pfizer, the NIH and other public/private biomedical research interests have complementary missions greater than the sum of their parts. Our hope is that this public/private initiative will encourage a deeper collective understanding of the genetic factors of disease for major new therapeutic advances.”

GAIN will be an FNIH-managed partnership that includes NIH, industry, foundations, individuals and advocacy groups. Governance will include an executive committee, a steering committee, as well as peer review and data access committees.

“Our partnership with pharmaceutical and biotech companies to speed up this research exemplifies the aim Congress had in mind when it established the Foundation for the National Institutes of Health to support the mission of NIH,” said John E. Porter, Vice Chairman of the foundation’s Board of Directors. “Through the financial support of the private sector, NIH will now be able to launch into this exciting initiative immediately. Moreover, the interaction of scientists from the public and the private sector dramatically increase the likelihood that this initiative will get off to a quick and efficient start that will genuinely produce important advances for all patients.”

Genetic Factors
The genetic analysis of both GAIN and GEI will focus on the alternative spellings — called single nucleotide polymorphisms or SNPs — that normally occur in the order of the 3 billion DNA base pairs or letters that make up a person’s genome. SNPs are like single-letter misspellings of a word. Most of these genetic variations are biologically meaningless. But a small fraction of these SNPs alter the function of a gene — often only slightly. The combination of many slightly altered genes may significantly increase the risk of a specific disease, but identifying such a complex set of genetics changes is challenging. Finding these disease-causing variants is one of the highest priorities of current biomedical research.

“Virtually all diseases have a hereditary component, transmitted from parent to child through the three billion DNA letters that make up the human genome,” said Francis S. Collins, M.D., Ph.D., Director of the National Human Genome Research Institute at NIH and chairman of the GAIN Steering Committee and co-chairman of the NIH Coordinating Committee for GEI. “But progress in identifying the genetic factors that influence health or disease, or even the response to treatment, is difficult. Both initiatives promise to rapidly identify the myriad genes in an individual that, taken together, contribute to an increased risk of illness — or that increase the chances of a healthy life. As the genetic underpinnings of health and common diseases become clearer, researchers will be empowered to develop targeted treatments that either prevent illness from occurring or treat it effectively once it does.”

There are about 10 million common SNPs in the human population. Scanning the genomes of large numbers of patients for such a large number of variants would be prohibitively expensive. Fortunately, a major shortcut has been discovered that reduces the workload about 30-fold. The International HapMap Project, led by the NIH and completed in October 2005, demonstrated that the 10 million variants cluster into local neighborhoods, called haplotypes, and that they can be accurately sampled by as few as 300,000 carefully chosen SNPs. New technological systems allow these SNPs to be systematically studied in high-throughput facilities that dramatically lower the cost.

For each study of 1,000 to 2,000 patients with a specific disease and a similar number of people who do not have the illnesses (controls), an investment of $3 million to $6 million (depending on the number of patients and controls) is needed for the first stage of genotyping. Follow-up studies to validate the results with additional patients and controls, data analysis, and patient management expenses will add to these basic costs. It is important to note, however, that these costs are a small fraction of what has already been invested in enrolling these study subjects, examining them, carrying out extensive laboratory investigations, and collecting their DNA.

The genotyping work itself will be performed by either commercial or government laboratories. The initial GAIN genotyping supported by Pfizer will be carried out by Perlegen Sciences, Inc., of Mountain View, Calif., and will start in late summer 2006; Pfizer is contributing these Perlegen-produced genotypes as an “in kind” donation to the project. A similar arrangement will be worked out with Affymetrix. Federally funded genotyping for GEI will be managed by an NIH coordinating committee under the usual government rules, subject to competition between research facilities, and begin in FY 2007.

The research will lead directly to the identification of major genetic susceptibility factors for common diseases of substantial public health impact — disorders such as heart disease, diabetes, cancer, stroke, Alzheimer’s disease, schizophrenia, osteoporosis, asthma, cataracts, hypertension, Parkinson’s disease, autism and obesity. The target diseases and the populations studied have yet to be selected and will be subject to a peer-review process.

Environmental Factors
Genes alone do not tell the whole story. Recent increases in chronic diseases like diabetes, childhood asthma, obesity or autism cannot be due to major shifts in the human gene pool. They must be due to changes in the environment, including diet and physical activity, which may produce disease in genetically predisposed persons. Therefore, GEI will also invest in innovative new technologies to measure environmental toxins, dietary intake and physical activity, and to determine an individual’s biological response to those influences, using new tools of genomics, proteomics and metabolomics.

“Differences in our genetic makeup certainly influence our risks of developing various illnesses,” said David A. Schwartz, M.D., Director of the National Institute of Environmental Health Sciences, also part of NIH, and co-chairman of the NIH Coordinating Committee for GEI. We only have to look at family medical histories to know that is true. But whether a genetic predisposition actually makes a person sick depends on the interaction between genes and the environment. We need better tools to evaluate environmental exposures, dietary intake and activity levels, and then to determine how those risk factors interact with specific genotypes to either maintain health or lead to disease. Without these more precise measures of exposure, it will be very difficult to figure out why certain people develop disease and others do not. We also need to find out why a disease has such a different prognosis from one person to the next. Given the recent advances in biomedical research, this is the right time to take on this challenge.”

To determine how the environment, diet and physical activity contribute to illness, investments will be made in emerging technologies, such as small, wearable sensors that can measure environmental agents that have contact with the body and individual measures of activity. Devices also will be developed that measure changes in human biology, which can be observed in samples of blood or urine. In aggregate, these new tests will provide the precision needed to help determine how these factors influence the genetic risk of developing disease. The goal is to produce devices for application to eventual population studies, to speed up data processing, to enhance accuracy and to reduce cost.

With the $14 million annual investment in the environmental component of this initiative, NIH will develop technologically advanced measures of dietary intake, precise personalized measures of physical activity, and biological measures that identify prior exposures to potential toxins such as metals and solvents. NIH also will assess disease indicators like inflammation and oxidative stress that are known to be influenced by environmental toxins.

The National Center for Biotechnology Information, a part of the National Library of Medicine at NIH, will develop databases to manage the vast amount of genetic, medical and environmental information that will emerge from these initiatives. To encourage rapid research advances, and in keeping with the principles pioneered by the Human Genome Project and increasingly common in such pre-competitive public/private partnerships, all data generated through these initiatives will be placed in the public domain.

Background information on whole genome association studies can be found at www.genome.gov/17516714. Background information on environmental impacts on health can be found at www.genome.gov/17516715.

Source: http://www.nih.gov

New drug 1D09C3 European orphan status

GPC Biotech AG (NASDAQ: GPCB) today announced that the Committee for Orphan Medicinal Products of the European Medicines Agency has recommended the granting of orphan medicinal product designation for the anticancer monoclonal antibody 1D09C3 for the treatment of multiple myeloma. The orphan drug status becomes effective when the European Commission has approved this recommendation. 1D09C3 is currently in a Phase 1 clinical program that is evaluating the antibody in patients with relapsed or refractory B-cell lymphomas, including Hodgkin’s and non-Hodgkin’s lymphomas, who have failed prior standard therapy.

1D09C3 was previously granted orphan medicinal product designation by the European Commission for Hodgkin’s lymphoma and chronic lymphocytic leukemia, a type of non-Hodgkin’s lymphoma.

1D09C3 is an anti-MHC (major histocompatibility complex) class II monoclonal antibody. 1D09C3 binds to MHC class II molecules on the cell surface and in preclinical studies appears to selectively kill activated, proliferating tumor cells, which include B-cell and T-cell lymphomas. In preclinical studies, 1D09C3 has been shown to induce programmed cell death and does not require a functioning immune system for its cell-killing effect. A Phase 1 clinical program evaluating 1D09C3 in patients with relapsed or refractory B-cell lymphomas who have failed prior standard therapy, is currently underway at several major cancer centers in Europe. 1D09C3 has been granted orphan medicinal product designation for the treatment of Hodgkin’s lymphoma and chronic lymphocytic leukemia. Additional information on 1D09C3 can be found in the Anticancer Programs section of the Company's Web site at www.gpc-biotech.com.

This press release may contain projections or estimates about plans and objectives relating to our future operations, products, or services; future financial results; or assumptions underlying or relating to any such statements. These statements are forward-looking and are subject to risks and uncertainties, many of which are beyond our control. Actual results could differ materially depending on a number of factors, including the timing and effects of regulatory actions, the results of clinical trials, the Company's relative success developing and gaining market acceptance for any new products, and the effectiveness of patent protection. There can be no guarantee that the Phase 1 trials with 1D09C3 will be successfully completed nor that 1D09C3 will be approved for marketing in a timely manner, if at all. We direct you to the Company's Annual Report on Form 20-F, as amended, for the fiscal year ended December 31, 2004 and other reports filed with the U.S. Securities and Exchange Commission for additional details on the important factors that may affect the Company's future results, performance and achievements. The Company disclaims any intent or obligation to update these forward-looking statements or the factors that may affect the Company's future results, performance or achievements, even if new information becomes available in the future.

Source: www.gpc-biotech.com

Comparison of diagnostic scans for MM

Comparison of Tc-99m sestamibi and F-18 FDG-PET in the assessment of multiple myeloma

BACKGROUND: Tc-99m methoxy-isobutyl-isonitrile (MIBI) has been reported to be a useful tracer in patients with multiple myeloma (MM). Few articles have reported the potential value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in the evaluation of MM. Therefore, the purpose of this study was to compare the diagnostic abilities of the MIBI scan and the FDG-PET scan in the evaluation of MM.

MATERIALS AND METHODS: Twelve patients with MM were included. All patients received a radiological skeletal survey, MIBI scan and FDG-PET scan.

RESULTS: Thirty-four lesions (19 soft tissue lesions and 15 skeletal lesions) plus 5 cases of bone marrow involvement were detected. The conventional skeletal X-ray survey detected 4 soft tissue lesions (21.1%), 12 skeletal lesions (80%), but no bone marrow involvement (0%). The MIBI scan found 4 cases of bone marrow involvement (80%), 13 soft tissue lesions (68.4%) and 12 skeletal lesions (80%). The PET scan detected 5 cases of bone marrow involvement (100%), 17 soft tissue lesions (89.5%) and 14 skeletal lesions (93.3%).

CONCLUSION: Both the MIBI and the FDG-PET scans are useful in the evaluation of patients with MM. However, FDG-PET can detect more lesions than the MIBI scan in patients with MM.

Hung GU, Tsai CC, Tsai SC, Lin WY
Department of Nuclear Medicine, Changhua Christian Hospital, Changhua, Taiwan
PMID: 16334169 [PubMed - indexed for MEDLINE]

Blimp-1 role in plasma cells

Long-lived plasma cells, residing primarily in the bone marrow, continuously secrete antibody and provide an important component of humoral memory. However, when such cells secrete autoantibodies or become transformed, they can be pathogenic. We have shown recently that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) is required for the formation of plasma cells. To determine what role Blimp-1 might play in maintenance of plasma cells, we generated mice in which the gene encoding Blimp-1 could be deleted in an inducible manner. Deletion of Blimp-1 either in vitro or in vivo leads to loss of previously formed B220(LO)CD138(HI) plasma cells. Using BrdU incorporation, we confirmed that Blimp-1 is required for the maintenance of nondividing, long-lived plasma cells in the bone marrow. Blimp-1 is also required for long-term maintenance of antigen-specific immunoglobulin in serum. Thus Blimp-1 is required not only for the formation but also for the maintenance of long-lived plasma cells. This finding provides the possibility of new drug design strategies for autoimmunity and multiple myeloma focused on blocking Blimp-1 expression or activity.

Shapiro-Shelef M, Lin KI, Savitsky D, Liao J, Calame K.Department of Microbiology, Columbia University College of Physicians and Surgeons, Columbia University, New York, NY 10032

Exp Med. 2005 Dec 5;202(11):1471-6. Epub 2005 Nov 28.PMID: 16314438

Treanda/Prednisone

According to an article recently published in the Journal of Cancer Research and Clinical Oncology, the chemotherapy agent Treanda™ (bendamustine) plus the steroid prednisone appears to provide superior outcomes to a standard treatment regimen consisting of the chemotherapy agent melphalan (Alkeran®) plus prednisone when used as initial therapy for multiple myeloma. Treanda is still in clinical trials and not yet approved in the U.S.

Treanda is a chemotherapy agent that is currently in phase II testing for several diseases. One advantage of Treanda is that it does not interfere with other commonly used chemotherapy agents referred to as alkylating agents. Treanda has been marketed and used clinically in Germany for many years in patients with NHL, chronic lymphocytic leukemia, multiple myeloma, breast cancer, and other solid tumors such as lung cancer.

Researchers from Germany recently conducted a clinical trial further evaluating Treanda in the treatment of multiple myeloma. This trial included 131 patients with newly diagnosed multiple myeloma who were treated with either Treanda plus prednisone or melphalan plus prednisone as initial therapy for their disease.

The combination of Treanda/prednisone appeared superior to melphalan/prednisone for this group of patients:

• The overall anticancer response rates were 75% for patients treated with Treanda/prednisone and 70% for those treated with melphalan/prednisone.
• The complete response rate (complete disappearance of detectable cancer) was 32% for patients treated with Treanda/prednisone, compared to only 13% for those treated with melphalan/prednisone.
• Maximum anticancer responses were achieved after approximately seven cycles of therapy in patients treated with Treanda/prednisone, compared with nearly nine cycles of therapy in patients treated with melphalan/prednisone.
• The average duration of time before treatment stopped working (treatment failure) was significantly longer for patients treated with Treanda/prednisone than for those treated with melphalan/prednisone.
• Quality of life, including pain, was significantly improved for patients treated with Treanda/prednisone compared to those treated with melphalan/prednisone.

The researchers concluded that treatment with Treanda/prednisone appears to provide superior outcomes (including quality of life) to melphalan/prednisone for patients with newly diagnosed multiple myeloma. However, further trials are necessary to confirm these findings. One disadvantage of Treanda over melphalan is that it requires intravenous administration, whereas melphalan is administered orally.

The researchers did recommend that based on these findings, Treanda/prednisone should be considered for initial therapy in patients with multiple myeloma who are not eligible for a transplant.

Reference: Ponish W, Mitrou PS, Merkle K, et al. Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone-a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). Journal of Cancer Research and Clinical Oncology. 2006 Jan 10;:1-8[Epub ahead of print].

Total U.S. cancer deaths drop

For the first time in more than 70 years, annual cancer deaths in the United States have fallen.

The number of cancer deaths dropped to 556,902 in 2003, down marginally from 557,271 the year before, according to the National Center for Health Statistics.

It's the first annual decrease in total cancer deaths since 1930, according to a cancer society analysis of federal death data. For more than a decade, health statisticians have charted annual drops of about one per cent in the cancer death rate -- the calculated number of deaths per 100,000 people.

But the actual number of cancer deaths still rose each year because the growth in total population outpaced the falling death rates.

In the U.S., experts are attributing the success to declines in smoking and the earlier detection and more effective treatment of tumours.

Death rates have fallen for lung, breast, prostate and colorectal cancer, according to American Cancer Society officials.

Those are the four most common cancers, which together account for 51 per cent of all U.S. cancer deaths.

The total number of cancer deaths among women actually rose by 409 from 2002 to 2003. Among men, deaths fell by 778, resulting in a net decrease of 369 total cancer deaths.

Cancer is diagnosed more often in older people than younger people, and the large and aging population of baby boomers may push cancer statistics a bit. Even so, that should be offset by treatment improvements and declines in smoking and cancer incidence.

Cataracts among cancer survivors

I was interested in this report, since after my chemo for my stem cell transplant, I was told I have the beginnings of cataract formation, and again every year since then. I had been told during my chemo treatment that cataracts are one of the many potential side-effects. I see an ophthalmologist annually in case of any vision problems.
***
OBJECTIVES: To determine the frequency of cataracts in cancer survivors and their association with patients' demographic characteristics, treatment, and cancer type and the perceived effect cancer had had on their overall health.

METHODS: This was a descriptive, cross-sectional review of the results of a survey of long-term cancer survivors who had been treated at the authors' institution.

RESULTS: Of 3936 respondents to the survey, 168 (4%) reported having had cataracts. Cataracts were most frequent in survivors of hematologic diseases (chronic leukemia, 17%; myeloma, 13%; acute leukemia, 9%; and lymphoma, 7%). There were no notable associations between cataracts and gender, age, ethnicity, marital status, education completed, or work status. Cancer survivors with cataracts were more likely to report that cancer had affected their overall health (56% vs 39%). There was a trend of association between cataracts and prior treatment with bone marrow transplantation, but not corticosteroids.

CONCLUSION: Cataracts affect a minority of long-term cancer survivors, but those who reported them were more likely to report that cancer had had a lasting effect on their overall health. Vision evaluation for all cancer survivors is recommended.

Stava C, Beck M, Vassilopoulou-Sellin R.Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Am J Clin Oncol. 2005 Dec;28(6):603-8.

PMID: 16317272 [PubMed - indexed for MEDLINE]

New drug AVN944

Avalon Pharmaceuticals, Inc. (Nasdaq: AVRX), a biopharmaceutical company focused on the discovery and development of small molecule therapeutics, today announced the completion of a three week dosing regimen on the first patient in Cohort II and the initiation of Cohort I of its Phase I clinical trial of AVN944 in patients with advanced hematological malignancies. The first patient in Cohort II, which is focused on multiple myeloma and lymphoma patients, completed the three week scheduled dosing at the University of Arkansas for Medical Sciences with no adverse side effects.

The Phase I clinical trial is designed as an open-label, repeat dose-escalation study for the evaluation of the safety and tolerability of AVN944 in adult patients with advanced hematological malignancies including those with leukemia, lymphoma or myeloma. The study is designed to determine the optimal dose with which to advance Phase II efficacy trials. In the current study, as many as 36 patients could receive AVN944 at or near this optimal dose. Currently, this trial is being conducted at four leading cancer centers in the United States, including the University of Arkansas for Medical Sciences, The University of Texas MD Anderson Cancer Center, Stanford University, and The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. Information on the trial, including other site locations when they initiate treatment, will be available at the National Institutes of Health clinical trial database at http://www.ClinicalTrials.gov.

AVN944 is an oral, small molecule inhibitor of the enzyme inosine monophosphate dehydrogenase (IMPDH), an enzyme that is essential for the de novo synthesis of the nucleotide guanosine triphosphate (GTP). AVN944 appears to inhibit cell proliferation by denying dividing cells of the GTP necessary for synthesis of DNA and RNA. IMPDH is highly upregulated in hematologic cancers and many other types of cancer cells are also sensitive to IMPDH inhibition.

AVN944 was in-licensed by Avalon from Vertex Pharmaceuticals Incorporated in February of 2005. Vertex conducted a Phase I trial in the U.K. in normal human volunteers where AVN944 was shown to be orally bioavailable and well-tolerated.

This announcement contains, in addition to historical information, certain forward-looking statements that involve risks and uncertainties, in particular, related to future clinical progress in the development of AVN944. Such statements reflect the current views of Avalon management and are based on certain assumptions. Actual results could differ materially from those currently anticipated as a result of a number of factors, risks and uncertainties including the risk that AVN944 will not progress successfully in its clinical trials, and other risks described in our SEC filings. There can be no assurance that such development efforts will succeed, that AVN944 will receive required regulatory clearance or, even if such regulatory clearance is received, that any subsequent products will ultimately achieve commercial success.

Source: http://www.avalonrx.com/

MPT treatment

Objectives: Thalidomide combined with conventional chemotherapies including oral melphalan shows significant anti-myeloma activity. To address this issue, feasibility and efficacy of a three drug combination consisting of intravenous (i.v.) melphalan, thalidomide and prednisone [M(i.v.)PT] was evaluated in advanced myeloma patients.

Patients and methods: Twenty-four advanced myeloma patients were treated with multiple cycles of a regimen consisting of low dose i.v. melphalan (20 mg/m(2)) at d 1, thalidomide at the dose of 50-100 mg/d given continuously and oral prednisone at the planned dose of 50 mg/d every other day. Intravenous melphalan was administered every fourth month. Median time from diagnosis was 40 months (range: 8-144 months). Fifteen patients (66%) had previously been treated with a combination of thalidomide and dexamethasone or with thalidomide alone.

Results: Overall, on an intent-to treat basis, 14 patients responded: three achieved near complete remission (nCR), seven achieved partial response (PR), four minimal response (MR). Six patients showed stable disease (SD) and four-disease progression. Interestingly, of five patients who had previously progressed while on thalidomide and prednisone, one reached nCR, two PR and one MR. After a median follow up of 14 months, median progression free survival was 9 months. Response duration was longer than that induced by the previous line of treatment in eight patients (33%). Thalidomide-associated toxicity mainly consisted of constipation, tingling and sedation.

Conclusions: M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.

Palumbo A, Avonto I, Bruno B, Ambrosini MT, Bringhen S, Cavallo F, Falco P, Boccadoro M.Divisione di Ematologia dell'Universita di Torino, Azienda Ospedaliera S. Giovanni Battista, Ospedale Molinette, Torino, Italy.PMID: 16438704 [PubMed - as supplied by publisher]