According to confirmation from the European Medicines Agency the benefit-risk balance for Revlimid (lenalidomide) remains positive within its approved patient population, however, doctors are advised of the risk of new cancers as a result of treatment with the medicine.
Revlimid is administered in combination with dexamethasone, an anti-inflammatory medicine, to treat adult patients with multiple myeloma whose disease has been treated at least once in the past.
The review of Revlimid was made after results of three new studies revealed a higher rate of new cancers in patients with newly diagnosed multiple myeloma. All patients were being treated with Revlimid and received other treatments concomitantly.
Researchers discovered a four-fold increase in the number of new cancers in patients being treated with Revlimid. The cancers included solid tumors and cancers of the blood and the immune system. Despite the fact that the studies were conducted in patients for whom Revlimid is not currently indicated, the Agency's Committee for Medicinal Products for Human Use (CHMP) raised concern regarding the result's relevance in the approved patient population.
They weighed the benefits of Revlimid against the risks in the approved patient population by reviewing all available data on new cancers in the approved population, including data from studies and post-marketing data. The study concluded that the risk of new cancers, such asskin cancers and some invasive solid tumors was observed in studies in the approved population. Investigators of the Committee also reviewed available data from the three studies in newly diagnosed multiple myeloma patients and concluded that Revlimid's benefits, in particular improved survival, continues to outweigh the risks. However, they recommend an update to Revlimid's prescribing information that should include a warning and advice to doctors on the risk of new cancers.
The Committee also reminds doctors that the current review of the benefits and risks of Revlimid only covers the approved patient population and does not cover its use outside of the current authorized indication. The Committee is now waiting for the European Commission to adopt their decision.
Written by: Petra Rattue
University of Southampton (England) researchers uncovered clues as to why several patients do not react to the standard drug for the blood cancer lymphoma, increasing optimism that additional effective treatments can be designed.
The study, which was co-funded by the charity Leukaemia & Lymphoma Research, the Medical Research Council, Cancer Research UK and Tenovus, Cardiff is published online in the medical journalBlood.
In the UK, non-Hodgkin's lymphoma is the sixth most common cancer, causing around 4,500 deaths annually in the country, with increasing cases being reported. Rituximab, which has been the most effective advance in treatment in recent years, works by tagging the surface of the tumor cells so they can be sought out and destroyed by the immune system of the patient.
Professors Mark Cragg, Peter Johnson and Martin Glennie and their teams at the University Of Southampton Faculty Of Medicine are researching explanations as to why an estimated 30% of people, sadly, do not react to treatment.
Researchers discovered that in some patients with lymphoma, after attaching to the surface of the cancer cells, rituximab is quickly internalized inside the cell, meaning the drug does not work as it's supposed to and immune cells can't seek out and destroy the cancer cells as efficiently.
Southampton scientists crucially observed, through a string of laboratory tests, that rituximab is internalized increasing faster by the lymphoma cells when a molecule called FcgRLLB is also present at high levels. Investigators discovered in a small preliminary analysis, that patients with high volumes of this molecule were less likely to be treated successfully. To confirm their discoveries, the scientists are proceeding with a larger analysis.
Professor Cragg explained:
"The discovery that high levels of FcgRllb on lymphoma cells can determine how effective rituximab will be could be very significant. It may be that different, non-internalizing antibodies are needed for certain patients. FcgRllb is also a potential target for new drugs to work alongside standard treatments."
Dr David Grant, Scientific Director at Leukaemia & Lymphoma Research, said:
"Treatment for non-Hodgkin's lymphoma has made rapid progress but clearly a significant number of patients do not respond to drugs like rituximab. Understanding exactly why they don't respond is vital so that new drugs can be designed to make sure that every patient survives."
Dr Ian Lewis, Associate Director of Research at Tenovus reported:
"In addition to helping us devise new drugs and therapeutic strategies for the treatment of lymphoma, this discovery could also help us to identify those patients who will not respond to treatment with rituximab and therefore offer them alternative, more effective treatments at a much earlier stage."
Leukaemia & Lymphoma Research has £3.7 million currently invested in 15 blood cancer research projects in Southampton.
Written by Grace Rattue
Adcetris (brentuximab vedotin), recently FDA approved for Hodgkin lymphoma and systemic anaplastic large cell lymphoma, may cost over $100,000 for a course of treatment, or $4,500 per vial. According to marketers and manufacturers, Seattle Genetics, patients typically need three vials in one dose, and from seven to nine doses per course of treatment - a cost range of from $94,500 to $121,500.
This is not the only drug to be approved recently with a huge price tag. Provenge, aprostate cancer vaccine, costs approximately $93,000 per course. Even though Provenge's marketers, Dendreon Corp. were happy with the its approval, the price tag sent its share price down as investors feared doctors may be concerned about being reimbursed - and as expected, sales were a disappointment.
According to Seattle Genetics, it expects some reimbursement issues when the product goes onto the market initially. However, the company insists its price is based extensive conversations with insurers, patients and doctors.
Savient Pharmaceuticals Inc. and Human Genome Sciences Inc. also had poor sales after being approved for expensive treatments.
According to the Wall Street Journal, Seattle Genetics' share price dropped 2.3% in afternoon trading on Nasdaq today. In the five years leading up to a recommendation for approval of Adcetris by an FDA Advisory Panel in July this year, the company's shares jumped fivefold. Adcetris is the first Hodgkin lymphoma medication to be approved in thirty years.
Market experts say that as brentuximab vedotin is designed to treat younger patients who rely on private insurance more than federal programs, the price tag may be less of an issue.
Even so, investors are much more interested these days on how many doctors will prescribe a new medication, how widespread reimbursement by insurance companies will be, and how much patients will benefit. Simply collecting data on a drug's effectiveness and showing how many millions have been spent on an experimental drug is not enough anymore.
Approximately 9,000 Hodgkin's lymphoma and 3,000 systemic anaplastic large cell lymphoma diagnoses are made annually in the USA.
Adcetris is a combination of a drug and an antibody - an antibody-drug conjugate. It allows the antibody to direct the drug on to a target in lymphoma cells, known asCD30. Adcetris is used to treat individuals with Hodgkin's lymphoma whose cancer has progressed after autologous stem cell transplant, or after two previous chemotherapy treatments (and the patient cannot receive a transplant). It may also be used in patients with systemic anaplastic large cell lymphoma whose cancer progressed after one treatment with chemotherapy.
Written by Christian Nordqvist
Researchers have found a gene defect that predisposes people to acute myeloid leukemia and myelodysplasia and hope their finding will lead to a genetic test that gives people with a family history of leukemia a chance to find out if they carry the faulty gene before their symptoms emerge. You can read a scientific paper on how Dr. Marshall S. Horwitz, professor of pathology at the University of Washington (UW) in the US, and colleagues, made their discovery, online in the 4 September issue of Nature Genetics.
Horwitz and colleagues comprise an international team of scientists and were able to carry out their research with the help of families from Australia, Canada, and the United States.
They discovered the mutations in a gene called GATA2, which among other roles, controls the process that changes primitive blood-forming cells into white blood cells.
The journey of discovery started after a research participant, a patient from central Washington, was successfully treated for leukemia in 1992 after receiving a bone marrow transplant at UW Medical Center. The patient's family history showed that several members had myelodysplastic syndrome, myeloid leukemia, and intractable mycobacteria infections, and prompted Horwitz to look for a genetic explanation.
Myelodysplastic syndrome (MDS) is where the body has problems producing certain types of blood cell. It starts with a fall in the quantity and quality of blood-forming cells in the bone marrow, the birthplace of blood cells. Patients often have severe anemia and need frequent blood transfusions.
Eventually the bone marrow fails and the blood count worsens, and about one third of patients with MDS develop acute myeloid leukemia (AML), where abnormal white cells accumulate in the bone marrow and screw up production of normal blood cells.
Linking up with colleagues in Australia, Horwitz heard of another family with a similar inherited blood disorder.
After 18 years of painstaking searching for candidate genes, the teams in the US and Australia eventually hit upon GATA2 as the gene whose mutations were most likely responsible for causing leukemia in the two families.
Since then, the researchers have identified faulty GATA2 mutations in more than 20 families and individuals.
In their paper they suggest the mutations could be more common than they first thought. For some, the GATA2 mutation leads to leukemia, but for others it could mean they are susceptible to dangerous bacterial, viral and fungal infections because of the shortage of white blood cells.
There have been a number of papers published recently implicating GATA2 in other diseases, including non-inherited leukemias, which are more common than the familial kind. And another paper in the same issue of Nature Genetics points to similar mutations in the gene being responsible for lymphedema and, in some cases, deafness.
What is puzzling is why similar gene mutations should cause such a range of health problems, and why it is so much harder to find genes for blood cancer than other cancers.
Horwitz told the press that while "several genes have been discovered and linked to solid, malignant tumors such as breast cancer in families susceptible to those types of cancer, so far very few inherited mutations have been uncovered for blood cancers."
Other studies have already linked mutations in the RUNX1 and CEBPA genes to inherited MDS and AML: these bind to DNA and control how it is transcribed to create the code that controls the production of proteins.
So for this study, the researchers looked at families that did not have the RUNX1 and CEBPA mutations and no other explanation for their inherited blood cancers: and this is how they came across GATA2. They also noticed that the mutations made the gene unable to play an effective role in producing healthy white blood cells.
Horwitz said the GATA2 mutations in the DNA sit next to an amino acid that is found to be faulty in some patients with terminal chronic myeloid leukemia. Being so near to each other on the DNA suggests the two locations share the same pathway that is important for several types of myeloid malignancies, said Horwitz.
The researchers hope their discovery will lead to a test where people at risk, because of the family history will be able to find out if they have the faulty GATA2 gene before any symptoms emerge. This could give them and their doctors a head start on getting an early diagnosis and treatment plan.
Another hope is that the discovery will also help the development of new therapies for AML and MDS and other blood disorders. A clinical trial to establish specific treatment options for people with GATA2 mutations is already under way in the US.
Grants from the National Institutes of Health in the US, the National Health and Medical Research Council of Australia, a Dora Lush Postgraduate Award, Leukaemia Foundation of Australia, the Cancer Council of South Australia, and MedVet Pty Ltd, helped pay for the research.
Written by Catharine Paddock PhD
Sprycel (dasatinib), a leukemia medication raises the risk of developing pulmonary arterial hypertension, the US Food and Drug Administration (FDA) announced today in aDrug Safety Communication. The FDA says doctors should check patients for signs and symptoms of underlying cardiopulmonary disease before considering prescribingSprycel - they should also evaluate patients during treatment.
Pulmonary arterial hypertension, also known as pulmonary hypertension orPAH is a kind of high blood pressure that only affects the arteries in the lung and the right side of the patient's heart. It starts when the pulmonary arteries and capillaries become narrowed, blocked or damaged, making it harder for blood to flow through the lungs. This raises pressure within the arteries in the lungs. Pressure builds up, making the right ventricle of the heart - the lower right chamber - have to work harder to pump blood through to the lungs. The heart muscle eventually weakens, and if left untreated may fail completely.
PAH is a serious illness that tends to get worse with time. PAH is potentially fatal.
Signs and symptoms of pulmonary arterial hypertension include fatigue, shortness of breath, swelling of the ankles and legs (and possibly other parts of the body), non-productive cough,angina pectoris, syncope, and in rare cases coughing up blood.
The FDA has received reports of patients who started on Sprycel developing PAH, in some cases after over a year on the medication. Some of the patients were on other drugs simultaneously, or had other underlying co-existing medical conditions. Some medical conditions may cause PAH-like symptoms. The FDA says that patients with symptoms who have other conditions ruled out, should be considered for a diagnosis of Sprycel-associated PAH.
If Sprycel-associated PAH is confirmed, the medication should be permanently discontinued, the FDA added.
The FDA stresses that if Sprycel treatment is discontinued, the PAH is reversible.
If you are a patient taking Sprycel and experience PAH-like symptoms, contact your doctor immediately.
The FDA is telling doctors that before initiating invasive procedures "more common etiologies of dyspnea associated with Sprycel therapy should be excluded, including pleural effusion, pulmonary edema, anemia, and lung infiltration."
Sprycel (dasatinib) has been on the market in the USA since June 2006. Since 2006, Bristol-Myers Squibb, the makers of the medication, have received cases of PAH. However, no deaths directly related to dasatinib usage have been reported.
The company received 12 cases of PAH which were confirmed by right heart catheterization (Sprycel most likely cause). In many cases patients were taking other medications and had other underlying medical conditions.
The FDA wrote on its website:
"There may be a combination of factors contributing to the development of PAH in patients taking Sprycel. In some cases, improvements in hemodynamic and clinical parameters were observed following discontinuation of Sprycel."
Patients and doctors are encouraged to report any serious problems to:
- Tel: 1-800-332-1088
- Fax: 1-800-FDA-0178
- MedWatch Online
- Regular Mail: Use postage-paid FDA Form 3500. Mail to: MedWatch 5600 Fishers Lane, Rockville, MD 20857
Dasatinib, chemical formula C22H26ClN7O2S, is an oral multi- BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia.
Written by Christian Nordqvist
