The American Society of Hematology - 48th Annual Meeting was held in Orlando, Florida; December 9-12, 2006. The following is a briefing of some of the articles presented at the conference.
Studies at cancer conference show new therapies changing outlook for blood cancer patients
Studies presented at the 2006 Annual Meeting of the American Society of Hematology
Orlando, FL and North Hollywood, CA, December 8, 2006 -- The International Myeloma Foundation (IMF) – conducting research and providing education, advocacy and support for myeloma patients, families, researchers and physicians – today noted that multiple studies presented at the 2006 Annual Meeting of the American Society of Hematology (ASH) illustrate the breadth of the gains being made in the treatment of multiple myeloma and related blood cancers. The findings show that new treatment regimens that began with THALOMID® and extend to both VELCADE® and the newest oral treatment REVLIMID® are helping a growing range of myeloma patients when used alone, sequentially and in various combinations. Collectively, these studies represent a significant increase in knowledge of how myeloma responds to treatment, which is already becoming applicable to other cancers.
The patient groups studied cover the full range, from relapsed patients to the newly diagnosed, young to old, and include patients with an otherwise poor prognosis due to chromosomal abnormalities. In some cases the data being presented at the conference significantly advances previous studies to show long-term response in newly diagnosed patients. In one of the most significant studies, researchers from the Mayo Clinic report 67% of patients using REVLIMID (plus the steroid dexamethasone) as primary therapy, achieved a response categorized as complete or very good, with a low rate of disease progression continuing even after two years.
"The many studies being presented at ASH not only confirm the good news we have been experiencing firsthand in our work with myeloma patients, but show that working with new classes of drugs is actually teaching us about treating cancer," said Brian G. M. Durie, M.D., myeloma specialist and chairman and co-founder of the International Myeloma Foundation. "We are learning to attack not just the cancer cell, but the environment in which it lives. We know that drugs like REVLIMID, for example, have multiple mechanisms of action, blocking the growth of tumor blood vessels, sensitizing the cancer cells to natural killer cells and suppressing TNF-alpha, a growth factor associated with inflammation. Understanding these mechanisms of action helps us increase the efficacy of our treatments, decrease their side effects, and apply them to a growing range of cancers including MDS, non-Hodgkins lymphoma and chronic lymphocytic leukemia."
In addition to the previously mentioned study from Mayo clinic, other key studies show that REVLIMID and VELCADE can be used together effectively even in patients who have already failed therapy on each drug alone. Studies cover long-term experience using each of THALOMID, REVLIMID and VELCADE in newly diagnosed patients, and possibly using them in various combinations as part of powerful new cocktail treatments. Also, studies from the IMF myeloma DNA-bank, Bank On A Cure®, look at the origins of side effects in some patients, while other groups use genetic profiling to better understand drug resistance.
"Blood cancers, including myeloma, are the third most common form of cancer, and today novel therapies are transforming the way we treat them," said Susie Novis, president and co-founder of the International Myeloma Foundation. "Studies presented at this meeting confirm our own experience as the premier organization dedicated to myeloma patient advocacy and support - while most cancer treatment benefits are measured in months, we are seeing many of our patients experience long-term responses measured in years and achieved without the ravages of chemotherapy. As a result, a growing number of myeloma patients are now able to live active, productive lives."
Myeloma, also called multiple myeloma, is a cancer of the bone marrow that affects production of red cells, white cells and stem cells. It is the second largest of the blood cancers affecting an estimated 750,000 people worldwide; in industrialized countries it is growing in number and affecting increasingly younger people.
Dr. Durie continued: "The wide range of presentations at ASH should enable us and our partners to continue to improve the outlook for our patients. This is perhaps the most encouraging meeting of ASH in the many years that I have been working in the myeloma field."
Soliris (eculizumab) data to be presented at American Society of Hematology
Abstracts including 'The terminal complement inhibitor eculizumab reduces thrombosis in patients with paroxysmal nocturnal hemoglobinuria' available
Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) today announced that abstracts relating to Soliris (eculizumab) for patients with paroxysmal nocturnal hemoglobinuria (PNH) have been published by the American Society of Hematology (ASH). Each of these abstracts will be presented at the 2006 ASH Annual Meeting in Orlando, Florida, December 9th to 12th by leading investigators in the Soliris (eculizumab) PNH clinical studies. Copies of the abstracts are available and can be viewed on-line through the ASH website:
www.hematology.org/meetings/abstracts.cfm. Access to the on-line abstracts may require registration, for which there is no charge.
The following abstracts will be presented in oral sessions:
- "The Terminal Complement Inhibitor Eculizumab Reduces Thrombosis in Patients with Paroxysmal Nocturnal Hemoglobinuria"
Dr. Peter Hillmen et al.
Time: Sunday, December 10th at 5:00pm
- "Treatment with the Terminal Complement Inhibitor Eculizumab Improves Anemia in Patients with Paroxysmal Nocturnal Hemoglobinuria: Phase III TRIUMPH Study Results"
Dr. Jorg Schubert et al.
Time: Sunday, December 10th at 5:15pm
The following abstracts will be presented in poster sessions:
- "Safety and Efficacy of the Terminal Complement Inhibitor Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: SHEPHERD Phase III Clinical Study"
Dr. Neal S. Young et al.
Time: Saturday, December 9th at 9:00am
- "Blockade of Intravascular Hemolysis in PNH with the Terminal Complement Inhibitor Eculizumab Unmasks Low-Level Hemolysis Potentially Occurring through C3 Opsonization"
Dr. Anita Hill et al.
Time: Saturday, December 9th at 9:00am Hall E-1
Mayo Clinic Cancer Center collaborating to find new tools to fight leukemia
ORLANDO, Fla. -- Mayo Clinic Cancer Center, working in collaboration with Ohio State University Comprehensive Cancer Center, presented evidence Sunday that a novel regimen of three chemotherapy drugs, pentostatin, cyclophosphamide and rituximab, resulted in significant clinical response in patients with previously untreated chronic lymphocytic leukemia (CLL). Lead researcher and Mayo Clinic hematologist Neil E. Kay, M.D., presented these findings at the 2006 American Society of Hematology Annual Meeting in Orlando.
"Chronic lymphocytic leukemia is incurable, but continues to be made more manageable with the advent of powerful new chemoimmunotherapy tools," says Dr. Kay. "We and our collaborators at Ohio State University, in particular Dr. Michael Grever, have done previous research on pentostatin that led us to believe there would be success with this regimen, and are pleased with the results."
Regimens using rituximab are common for CLL patients, says Dr. Kay, and his team decided to build upon that knowledge and their understanding of the highly potent chemotherapeutic antibiotic pentostatin to try to develop an even better treatment option. The investigators initiated a trial of three weeks (one cycle) of combined chemotherapy drugs pentostatin (P), cyclophosphamide (C) and rituximab (R) repeated in six cycles for 64 symptomatic but previously untreated patients. Patients in the study also received one year of prophylactic sulfamethoxazole-trimethoprim (anti-infection drug) and acyclovir (antiviral drug) along with the PCR treatment.
The researchers reviewed study participants’ prognostic status and divided the patients into risk categories at the beginning of the study, using a number of different prognostic evaluation tools to describe them, including the Rai stages (clinical levels of disease progression), CD38 and ZAP-70 (overexpressed proteins found in CLL cells), IgVH (mutational status of the immunoglobulin gene occurring in CLL patients), and FISH panel assessments (fluorescent probes on the chromosomes to determine common recurring genetic mutations in CLL). The majority of the patients were in high-risk categories; they had significant disease progression and/or a high expectation of rapid advancement of disease.
Following treatment, Dr. Kay’s team found that 91 percent of the patients experienced positive clinical responses (experienced improvement in their condition) to the treatment based on the National Cancer Institute’s Working Group criteria for responses. Forty-one percent achieved complete response, 22 percent experienced nodular partial response and 28 percent partial response, with the average patient’s disease currently estimated to being in response for 32.6 months. The researchers also found that bone marrow suppression and/or infections were minimal.
The prognostic variables that normally indicate likelihood of poor response to treatment appeared to be negated by the treatment --only one genetic defect (deletion of the p arm of chromosome 17) was found to prevent complete response or nodular partial response; the other risk factors did not diminish treatment effectiveness. Also, the researchers found that the regimen was equally effective in young and elderly (over age 70) patients.
"We are very pleased with the results of this study," says Dr. Kay. "This is a new, viable option for high-risk patients who might not have had much hope before, and it’s especially exciting that it works for patients of all age groups."
Chronic lymphocytic leukemia is a blood and bone marrow cancer that affects 10,000 new patients each year in the United States. It is called chronic leukemia because it progresses more slowly than acute leukemia, and lymphocytic because it affects a group of white blood cells (lymphocytes), an important component of the immune system which typically fights infection.
Drug combination proves effective against myeloma in Phase I trial
BOSTON—Two "new generation" drugs for the bone marrow cancer multiple myeloma may work even better together than they do individually, according to the results of a multicenter Phase I clinical trial to be presented by Dana-Farber Cancer Institute scientists at the annual meeting of the American Society of Hematology in Orlando, Fla.
The trial – the first and largest reported to date to test the drugs bortezomib (Velcade) and lenalidomide (Revlimid) in combination – involved 38 myeloma patients whose disease had recurred after previous treatment and was progressing despite other therapies.
Participants were divided into groups that received successively higher doses of the drugs. Some also received dexamethasone, a standard myeloma medication which adds to the effects of both bortezomib and lenalidomide, if the combination alone no longer controlled their disease.
The researchers, led by Paul Richardson, MD, and Ken Anderson, MD, of Dana-Farber, found that 58 percent of 36 evaluable patients responded to lenalidomide and bortezomib, including six percent who had complete remission, despite being heavily pre-treated and, in most cases, having received both classes of drug before. The median length of remission was six months, with some patients having disease control for up to two and a half years. The combined therapy also produced only mild fatigue or peripheral neuropathy (nerve damage signaled by tingling or numbness), researchers found. Patients who received dexamethasone because their disease continued to progress on the drug combination found the additional drug tolerable, and it produced a response or disease stabilization in about three quarters of them.
"It is remarkable to see the combination prove both tolerable and engender such durable responses in resistant disease," Richardson says. "We are hopeful that this combination will prove to be a key therapeutic backbone in improving outcomes for our patients, both early and later in their course."
Both Velcade and Revlimid are relatively recent additions to doctors' arsenal against multiple myeloma. Velcade thwarts myeloma cells by interfering with their ability to break down and dispose of certain proteins. Revlimid also attacks the tumor cells directly and disrupts their interactions with surrounding tissue in the bone marrow.
The trial was based on preclinical work that found Revlimid increases myeloma cells' vulnerability to Velcade and dexamethasone, which suggested that patients might benefit from a combination of them. The encouraging results of the Phase I study have prompted investigators to begin Phase II trials of the combined therapy in patients with newly diagnosed myeloma and in hard-to-treat, relapsed cases. Phase III trials are also planned.
Clinical study results using Aldagen's product to isolate cord blood stem cells presented at ASH
Improved safety and efficacy seen when using ALDESORT compared to COBLT control group
Durham, NC -- December 11, 2006 – Aldagen, Inc. today announced the presentation of data from a clinical trial using its ALDESORT® product to isolate stem cells from cord blood. The trial is being conducted by Joanne Kurtzberg, MD, the Duke University physician who pioneered the use of umbilical cord blood as a treatment for fatal childhood cancers and genetic diseases in 1993. Dr. Kurtzberg presented positive interim results of the study at the 48th Annual Meeting of the American Society of Hematology in Orlando, Florida.
About the Study
ALDESORT enriches a unique population of stem and progenitor cells from cord blood that contribute to neutrophil and platelet engraftment and to immune reconstitution following transplantation. The primary goal of the clinical study is to determine if transplanting these enriched cells is safe. The study will also indicate if transplanting these cell populations could result in accelerated engraftment and lead to more favorable clinical outcomes compared to a historical control group from the Cord Blood Transplantation Trial (COBLT) study, a multicenter Phase II study sponsored by the National Heart, Lung and Blood Institute. At the time of the interim analysis, eleven pediatric patients with cancer or genetic diseases were transplanted with unrelated donor umbilical cord blood and a supplement of cord cells isolated using ALDESORT. Overall survival at 180 days was 90.9%, compared to an overall survival at 180 days of 57% in COBLT study. The cumulative incidence of neutrophil engraftment by day 42 was 90.9% (p=0.001) and platelet engraftment by day 100 was 79.5% (p=0.003).
“The findings of this study once again show the promise of transplanting stem cells from umbilical cord blood to treat children with resistant cancers and genetic diseases,” said Dr. Kurtzberg. “The infusion of cells enriched with ALDESORT has had no adverse effects and appears to improve the speed and efficacy of cord blood transplantations.”
About Cord Blood Transplants
Umbilical cord (UBC) stem cells are located in the umbilical cord and placenta of a newborn at birth. After the baby has been delivered and the umbilical cord has been cut, blood is drawn from the umbilical cord. It is a completely non-invasive procedure with absolutely no risk to either mother or child. Umbilical cord stem cells are not embryonic stem cells. More than 4000 cord blood transplantations have been performed worldwide. Dr. Kurtzberg and her team at Duke University have treated and saved more children with cancers and rare genetic diseases than any other center in the world.
Aldagen’s ALDESORT product is a set of proprietary reagents that can be used with currently available cell sorting systems to isolate a highly potent population of stem and progenitor cells from human bone marrow, peripheral blood and cord blood. The unique chemistry incorporated into the ALDESORT product allows the isolation of stem and progenitor cells based on the elevated expression of an intracellular enzyme, aldehyde dehydrogenase (ALDH).
Positive clinical trial results of investigational thrombocytopenia agent
AkaRx Inc. presents Phase I clinical data of AKR-501 at 48th American Society of Hematology Meeting
ORLANDO, Fla., Dec. 11 -- AKR-501 is a promising member of a new class of agents called, “TPO receptor agonists” that is now in Phase II clinical development. It is an investigational orally administered drug being developed by AkaRx, Inc. intended to mimic the biologic effect of thrombopoietin, a growth factor that stimulates production of platelets.
At the American Society of Hematology meeting, results from two Phase I clinical research trials were presented. These data in healthy volunteers showed that AKR-501 produced a 50% increase or greater over the baseline platelet count. AKR-501 is the first oral drug in its class to show these platelet increases with a single dose. In the single dose study this was achieved at the 100 mg dose. In all volunteers given multiple doses of either 10 mg or 20 mg for 10 – 14 days a platelet effect was observed where increases were at least 50% over baseline.
The unmet medical need for AKR-501 is that there is no approved agent to specifically stimulate megakaryocytes to produce platelets to treat thrombocytopenia in the same way that there are products available to stimulate production of red and white blood cells. Severe thrombocytopenia is currently managed in some settings with platelet transfusions. However, this temporary solution in not suitable for long-term use in chronic settings and is often associated with serious complications when used in acute situations. AKR-501 imitates the body’s mechanism for stimulating platelet production by mimicking the action of thrombopoietin—the growth factor that modulates this process.
“AKR-501 is a very promising candidate for use in the prevention and treatment of thrombocytopenia in a host of diseases, among them, ITP, Chemotherapy Induced Thrombocytopenia, and Hepatitis C associated thrombocytopenia,” said Robert E. Desjardins, MD, President and CEO of the drug development company, AkaRx. “These are the first clinical results of AKR-501 that show that it may be a safe thrombopoietic agent with an impressive ability to stimulate platelet production. This class may be a real breakthrough for patients. These results for AKR-501 give us confidence to envision a very broad clinical development program across the world for this compound that appears to have great medical and commercial potential.”