BOULDER, Colo., Dec. 13 /PRNewswire-FirstCall/ -- Pharmion Corporation reported today on data abstracts from studies investigating the role of thalidomide as a treatment option for all stages of multiple myeloma. Results of these and numerous other thalidomide studies were presented at the American Society of Hematology (ASH) 47th Annual Meeting and Exposition in Atlanta (December 10-13, 2005).
Data Analysis Highlights Thalidomide Activity in Patients with Newly Diagnosed Multiple Myeloma (abstracts 779 and 780)
An analysis of data from a multi-center trial of 255 patients comparing the efficacy and toxicity of the combination of oral melphalan and prednisone (MP) to MP plus thalidomide (MPT) in newly diagnosed multiple myeloma (MM) patients older than 65 years of age was presented in an oral session on Tuesday, December 13. Patients treated with MPT experienced overall response rates of 76 percent vs. 48 percent for MP alone (p<.0001), and near- complete response rates of 28 percent vs. 7 percent, respectively (p<.0001). MPT patients also had better outcomes with regard to median progression-free survival (33 months vs. 14 months, (p<.001)) and two-year survival rates (82 percent vs. 65 percent (p=.02)). Looking at only those patients who completed the assigned six cycles in both study arms, the two-year survival rate was 90 percent for the MPT arm vs. 71 percent for patients given MP, a statistically significant difference (p<.01). Grade III/IV adverse events were reported in 49 percent of MPT-treated patients vs. 25 percent of those treated with MP; they included thromboembolism, infections and peripheral neuropathy.
Data from a second multiple myeloma study in newly-diagnosed elderly patients presented in an oral session on December 13 demonstrated differences in overall survival, response to treatment and progression-free survival (PFS). Patients aged 65-75 were given either MPT, MP or autologous stem cell transplantation (MEL100). The study compared MPT vs. MP, MP vs. MEL100, and MPT vs. MEL100. Analysis of data from 436 patients, 191, 124 and 121 in MP, MPT and MEL100 groups, respectively, showed that following a median follow-up time of 32.2 months, the PFS time was significantly longer in the MPT as compared to the MP patient group (27.6 months for MPT and 17.1 for MP, p<.0001). No significant difference was seen between the MP and MEL100 groups (RR=1.2, p=0.12). Based on the superior results for the MPT arm, enrollment was stopped after this analysis. The investigators conclude, based on this data, that the reference treatment for newly diagnosed multiple myeloma patients, ineligible for high-dose therapy, should be MPT.
“In both of these trials, the addition of thalidomide to the standard melphalan-prednisone regimen represents a significant clinical benefit to elderly, newly-diagnosed multiple myeloma patients,” said Antonio Palumbo, MD, lead investigator and presenter, Divisione di Ematologia dell’Universita di Torino, Italy. “These data suggest that thalidomide, which is widely used in relapsed/refractory myeloma, may serve a promising role in first-line therapy as well.”
Study Assesses Thalidomide Combination Therapy in Newly Diagnosed Patients (abstract 782)
An interim analysis of response rates from a study of previously-untreated elderly patients with multiple myeloma was presented in an oral session on Tuesday, December 13. A total of 125 evaluable patients, randomized to receive either thalidomide-dexamethasone (TD) or melphalan-prednisone (MP), demonstrated a overall response rate (ORR) of 67 percent for the TD arm vs. 48 percent on MP (p<.05). Analysis per protocol revealed an ORR of 89 percent in the TD arm and 66 percent in the MP group (p=.02). Data from these patients demonstrate a significantly shorter time to response and time to best response in the TD group as compared to the MP group (8 and 11 weeks for TD vs. 10 and 39 weeks for MP, p=.01 and p=.0047, respectively). Grade III/IV thrombocytopenia was more frequent and leucopenia was more statistically significantly more common in the MP group.
Data Highlight Results from Total Therapy 2 Trial in First Line MM Patients (abstract 423)
Data from a prospective, randomized study of 668 patients were presented in an oral session on Monday, December 12. This study examined the impact of adding thalidomide (T) to melphalan (MEL200)-based tandem autotransplants for multiple myeloma. While the addition of thalidomide did not significantly extend overall survival, potentially due to an imbalance of cytogenetic changes between the two arms, it did significantly increase complete response rates (41 percent with MEL200 alone vs. 59 percent with MEL200 plus T, p=.001). In addition, patients receiving thalidomide with MEL200 demonstrated improved five-year event-free survival rates (42 percent for MEL200 vs. 54 percent for MEL200 plus T, p=.017).
Data Assess Impact of Thalidomide Maintenance Therapy Following Autologous Transplantation in Multiple Myeloma (abstract 1148; poster session 306-I)
Interim data from 593 patients (under age 65) in a study assessing the role of thalidomide maintenance therapy among multiple myeloma patients receiving high-dose chemotherapy and autologous stem cell transplant were presented in a poster session on Saturday, December 10. In the study, designed to examine duration of response after high-dose VAD therapy, patients received two autologous transplants (with melphalan doses of 140mg/m2 and 200mg/m2, respectively); those without progressive disease after two months were randomized to receive no maintenance (arm A), pamidronate maintenance (arm B), or pamidronate maintenance with thalidomide (arm C). At the time of this analysis, the four-year overall survival was similar for the three treatment groups; however, the data also demonstrate that the four-year post-diagnosis probability of event-free survival was 39 percent for patients in arm A, 37 percent in arm B and 50 percent for arm C (p<.02). The benefit was particularly pronounced among patients with a beta-2-microglobulin >2.5mg/l without deletion of chromosome 13.
“Following a single or double autologous transplant, nearly all multiple myeloma patients ultimately relapse,” said Pr Michel Attal, MD, lead investigator, Service d’Hematologie, Hopital Purpan, Toulouse, France. “This study demonstrates that the addition of thalidomide to this therapy may help manage residual disease and reduce the frequency of relapse.”
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 50mg 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 50mg 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.
About Pharmion
Pharmion is a pharmaceutical company focused on acquiring, developing and commercializing innovative products for the treatment of hematology and oncology patients in the U.S., Europe and additional international markets. For additional information about Pharmion, please visit the company’s website at www.pharmion.com.
For more information or complete prescribing information about Vidaza, please call 1-866-PHARMION.
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