Dr. Brian Durie, Chairman and Medical Director of the International Myeloma Foundation, will host a teleconference next week to highlight key myeloma presentations at the upcoming American Society of Hematology Annual Meeting. The teleconference will take place on Monday, November 30th at 11 a.m. ET.
Discussion topics will include:
§ Treating the full cycle of myeloma
§ Pipeline drugs – what’s next and why they’re needed
§ Genetic variations in survival and outcome
Here are the dial-in details for the teleconference:
800.860.2442 (U.S.) or 412.858.4600 (outside of the U.S.)
Pass code: IMF
Genetic variants in the DNA of patients with multiple myeloma appear to strongly influence survival, a groundbreaking new genomic study has concluded.
In this first pass at identifying genetic markers for survival, treatment response, and complications in the disease, a group of 3,400 variants predicted early or late mortality 76% of the time, Dr. Brian Van Ness said in an interview about the initial report (BMC Medicine 2008 Sept. 8 [doi: 10.1186/1741-7015-6-26]).
“Clearly, inherited genetics influenced survival,” said Dr. Van Ness
of the University of Minnesota, Minneapolis. “What we have not yet done is identify which specific variants are responsible for these differences. Our hypothesis is that it won’t be a single variant driving response or survival, but a complex interaction of many.”
After narrowing down the initial 3,404 candidate single nucleotide polymorphisms (SNPs), Dr. Van Ness and his colleagues are now focusing on 1,000 SNPs found to be most strongly associated with the outcome
measures. More studies are on the way using this genetic panel, he said.
Indeed, just 2 weeks after the first study appeared, a coinvestigator, Dr. Gareth Morgan of London’s Royal Marsden Hospital, published findings on the association between certain SNPs and the incidence of
treatment-associated venous thromboembolism (VTE). The analysis showed that some of the variants associated with thalidomide-related VTE occurred in pathways important in drug transport and metabolism.
“The effects of the SNPs associated with thalidomide-related VTE may be functional at the level of the tumor cell, the tumor-related microenvironment, and the endothelium,” Dr. Morgan and his colleagues wrote (Blood 2008 Sept. 19 [Epub ahead of print]).
“Another study, currently submitted, has identified an association between some of the variants and the development of severe myeloma bone disease,” Dr. Van Ness said.
The initial investigation used a genetic screen developed from two DNA data sets: cells from the Coriell Institute for Medical Research, and samples obtained from multiple myeloma patients enrolled in two
randomized drug trials, as well as some unaffected spouses. The samples came from white, black, Hispanic, and Asian patients from North America and Europe. The candidate SNPs, occurring on 983 genes, were chosen based on the most recent genetic research and included on a myeloma-specific gene-testing chip.
The investigators chose extremes of survival as the first test of the panel, because this comparison was most likely to show the effects of any genetic variant. “We took the worst outcomes – people who died in
the first year of their disease – and the best outcomes – those who survived at least 3 years without progression,” Dr. Van Ness said. After repeatedly running the screen on both data sets, the team concluded that, as a whole, it discriminated the survival groups correctly 76% of the time.
Further drilling down identified several SNPs of particular interest, including some associated with drug metabolism, transport, and export; a variant that induces myeloma apoptosis; one associated with cellular
migration and angiogenesis; and several linked to proliferative responses.
Although not designed to detect racial differences, the initial screen did identify some interesting variations: 401 of the SNP variants occurred only in black patients. In whites, there was no difference in these SNPs between cases and controls.
“We know that African Americans have a two- to threefold increase in the incidence of myeloma, but we don’t yet know why,” Dr. Van Ness said. “We’ll be trying to identify those genetic variants that might uniquely increase the risk for one race to develop myeloma over another.”
Neither this initial analysis nor subsequent ones will examine the possible interplay of environment with genetics. But, Dr. Van Ness said, such studies may be forthcoming. The International Myeloma Foundation of North Hollywood, Calif., is conducting a patient survey to begin assessing what role – if any – environmental exposure plays in disease development. The 36-page survey asks patients to detail their environmental, dietary, and geographical exposures. The National Cancer Institute will collaborate with the group in evaluating the data.
The International Myeloma Foundation is also the curator of the DNA samples used in the analysis through its Bank on a Cure program. “Bank on a Cure was developed by an international group of physicians and scientists to deal with a disease that’s difficult to deal with,” Dr. Van Ness said. “It’s not a high-incidence cancer, so it’s not easy to research.”
The Bank on a Cure group developed cooperative agreements with national and international clinical trial groups, and the studies were funded by the International Myeloma Foundation. While exploration of genetic variants relevant to multiple myeloma is in its infancy, Dr. Van Ness predicted the effect could be profound.
This is a press release from the International Myeloma Foundation.
I was on Revlimid with high dose dex for some time back in 2005, I think. I remember being miserable on the high doses of steroids and that my MM progressed after I cut back. We figured the Revlimid didn’t work for me. But that doesn’t mean that it might not work if I added Biaxin. It’s one more thing I can try when I have to start treatment again. The thought of having to take steroids again kind of causes a feeling of anxiety.
–BiRD Study (Biaxin®-Revlimid-Dexamethasone) Provides Evidence of Deep Complete Response Rates In Newly Diagnosed Multiple Myeloma–
North Hollywood, CA, January 4, 2008 – The International Myeloma Foundation (IMF)—supporting research and providing education, advocacy and support for myeloma patients, families, researchers and physicians—today said updated data from the Phase II BiRD study provide a new option for newly diagnosed patients with multiple myeloma whether or not they proceed to stem cell transplant. The findings show a superb overall response rate of 90.3%. 38.9% of the patients achieved a complete response (using EBMT criteria) and 73.6% achieved a 90% or greater decrease in m-protein levels. Using the new International Myeloma Working Group Criteria—recently developed to better define the magnitude of a complete response by a panel of experts led by Brian G.M. Durie, M.D., chairman and co-founder of the IMF—30.6% of the patients achieved this new stringent complete response* (sCR). The findings have been published in the online version of the journal BLOOD.
The BiRD regimen is made up of REVLIMID® (lenalidomide) plus a low dose of the steroid dexamethasone, and adds Biaxin® (clarithromycin). The BiRD treatment did not impede stem cell transplantation, and demonstrated two-year event-free survival rate of 85.2% for patients who underwent stem cell transplant and 75.2% for those who continued on therapy without transplant. Median event-free survival time was not reached.
In addition to the response criteria, the findings from the BiRD study, like a previous study of REVLIMID with low-dose dexamethasone, show response deepening over time: the average time to partial response was just over six weeks, but average time to complete response was 22 weeks, and stringent complete response was reached at 38 weeks.
"This is an exciting time for the treatment of myeloma," said Susie Novis, president and co-founder of the IMF. "We now have multiple studies showing improved response and survival with various regimens including REVLIMID/dexamethasone in previously treated and newly diagnosed patients, DOXIL®/VELCADE® for previously-treated patients who want a steroid-free regimen, and thalidomide/melphalan/prednisone in older patients not eligible for transplant."
Myeloma, also called multiple myeloma, is a cancer of the bone marrow that affects production of red cells, white cells and stem cells. It affects an estimated 750,000 people worldwide, and in industrialized countries it is being diagnosed in growing numbers and in increasingly younger people.
The data were published in an article by lead author Ruben Niesvizky of the Multiple Myeloma Service, Division of Hematology and Medical Oncology, Weill-Cornell Medical College, New York Presbyterian Hospital-Cornell Medical Center.
* sCR requires complete absence of M-protein by immunofixation, normal free light chain ratio and a negative marrow biopsy by immunohistochemistry.
ABOUT THE INTERNATIONAL MYELOMA FOUNDATION
The International Myeloma Foundation is the oldest and largest myeloma organization, reaching more than 165,000 members in 113 countries worldwide. A 501 (c) 3 non-profit organization dedicated to improving the quality of life of myeloma patients and their families, the IMF focuses in four key areas: research, education, support and advocacy. To date, the IMF has conducted more than 120 educational seminars worldwide, maintains a world-renowned hotline, and operates Bank on a Cure®, a unique gene bank to advance myeloma research. The IMF was rated as the number one resource for patients in an independent survey by the Target Research Group. The IMF can be reached at (800) 452-CURE, or out of the United States at (818) 487-7455. More information is available at www.myeloma.org.
Media Contact: Stephen Gendel or Jennifer Anderson (212) 918-4650