my personal edition > haematology other > news


  E-Mail this DGNews to a colleague

DGNews

Addition of Thalidomide to Standard Therapy Improves Overall Survival in Newly Diagnosed Multiple Myeloma

Data presented at plenary session at the American Society of Clinical Oncology 42nd Annual Meeting

BOULDER, CO -- June 15, 2006 -- Pharmion Corporation reported that data presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta, GA (June 2-6, 2006) demonstrates that the addition of thalidomide to standard therapy improves overall survival in patients with newly diagnosed multiple myeloma.

Data from a three-arm study, which was supported by Pharmion, in newly diagnosed, elderly (>65 years) multiple myeloma patients were presented at a plenary session on Sunday, June 4. The study was designed to compare overall survival in patients receiving standard therapy of melphalan and prednisone (MP), or standard therapy plus thalidomide (MP-T) or a combination of chemotherapies (vincristine/adriamycin/dexamethasone, or VAD) followed by melphalan and transplantation (MEL 100). A total of 447 patients were randomized to one of the three treatment arms.

Thalidomide was administered at doses up to 400 mg according to patient tolerability. Following an August 2005 interim analysis, recruitment was stopped on the recommendation of the study's Data Safety Monitoring Board (DSMB).

At the time of analysis, the median overall survival in the MP-T arm was approximately 54 months, compared to 32 and 39 months, respectively, for the MP and MEL 100 arms. Thalidomide treatment was well-tolerated by the majority of patients. Thalidomide in combination with other treatments was associated with more venous thrombosis and pulmonary embolism. Patients taking thalidomide were also at more risk of peripheral neuropathy, neutropenia and constipation.

"These results are extremely encouraging news for patients with multiple myeloma," said Professor Thierry Facon, from the Intergroupe Francophone du Myelome (IFM) and lead investigator of the study. "The study results confirm thalidomide as a beneficial treatment for newly-diagnosed multiple myeloma. Although current treatments can help to a certain extent, new treatments are still desperately needed for these patients and the results of this study show thalidomide could play an important role in helping patients to live longer," he added.

"These powerful data represent a paradigm shift in the treatment options for newly diagnosed multiple myeloma patients," said Patrick J. Mahaffy, chief executive officer of Pharmion. "We look forward to working closely with the IFM and the EMEA to gain regulatory approval for thalidomide and to make this important treatment option available for patients in Europe," he added.

Thalidomide Regulatory Status
The U.S. Food and Drug Administration (FDA) recently approved thalidomide, in combination with dexamethasone, for the treatment of newly-diagnosed multiple myeloma. However, the drug remains unapproved in Europe. Pharmion estimates that multiple myeloma affects approximately 82,000 people across Europe.1

Pharmion is planning to submit a Marketing Authorization Application for thalidomide in the treatment of multiple myeloma to the European Medicines Agency (EMEA) by early 2007. The Company expects this application will include data from four phase 3 clinical studies in patients with newly diagnosed multiple myeloma:

IFM clinical study: melphalan/prednisone compared to melphalan/prednisone plus thalidomide or autologous stem cell transplantation GIMEMA clinical study: melphalan/prednisone compared to melphalan/prednisone plus thalidomide ECOG clinical study: thalidomide/dexamethasone compared to dexamethasone

A pivotal study sponsored by Celgene and supported by Pharmion: thalidomide/dexamethasone v dexamethasone

About Thalidomide Pharmion
Thalidomide Pharmion is approved in Australia, New Zealand, Turkey and Israel for the treatment of multiple myeloma after the failure of standard therapies and the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Thalidomide is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. Thalidomide is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.

Following the Australian registration in October 2003, Pharmion received approvals for Thalidomide Pharmion 50 mg hard capsules for the same indications in New Zealand (December 2003), Turkey (June 2004) and Israel (September 2004).

As a condition of registration, the Pharmion Risk Management Program (PRMP) is mandatory in Australia, New Zealand, Turkey and Israel. Prescribers and pharmacies are required to register with the PRMP in order to prescribe or dispense thalidomide, and patients are required to complete an informed consent process and to participate in a confidential surveillance registry. The PRMP is based on the S.T.E.P.S.TM program developed by Celgene Corporation in cooperation with the US Food and Drug Administration.

Safety Notice
If thalidomide is taken during pregnancy, it can cause severe birth defects or death to an unborn baby. Thalidomide should never be used by women who are pregnant or who could become pregnant while taking the drug. Even a single dose, one capsule (50 mg), taken by a pregnant woman can cause severe birth defects. Because thalidomide is present in the semen of male patients, males receiving thalidomide must always use a condom during sexual contact with women of childbearing potential even if he has undergone a successful vasectomy.

Thalidomide Pharmion 50 mg hard capsules will only be available under a special restricted distribution program. This program is called the Pharmion Risk Management Programme (PRMP). Under this program, only registered prescribers and pharmacists may dispense the drug. In addition, patients must be advised of, agree to and comply with the requirements of PRMP.

Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, side effect of treatment with thalidomide that may be irreversible. The most commonly observed adverse reactions associated with the use of thalidomide are constipation, somnolence and asthenia.

The other clinically most important adverse reactions associated with the use of thalidomide include orthostatic hypotension, decreased white blood cell counts including neutropenia, severe skin reactions including Stevens Johnson Syndrome and toxic epidermal necrolysis, headache, rash, eosinophilia, peripheral oedema, dyspnoea, dizziness, hypotension, bradycardia, symptomatic hypothyroidism, increase or decrease in platelet count, anaemia and, in HIV patients, an increase in HIV viral load.

Seizures, including grand mal convulsions, have been reported very rarely during the use of thalidomide in clinical practice. It has been suggested that thalidomide's anti-angiogenic properties may interfere with wound healing. Patients should be advised about associated adverse events and routinely monitored by a physician during treatment with thalidomide.

About ENL
ENL is a severe and painful complication of leprosy. Thalidomide has been used to treat ENL patients in the U.S. for more than twenty years through a U.S. Public Health Service compassionate use program.

About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease is unknown.


SOURCE: Pharmion

E-Mail this DGNews to a colleague

To print, use this version