Data presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta demonstrates that the addition of thalidomide to standard therapy improves overall survival in patients with newly diagnosed multiple myeloma. These data from a three-arm phase III study in newly diagnosed, elderly multiple myeloma patients were presented at an ASCO plenary session.
The study was designed to compare overall survival in patients receiving standard therapy of melphalan and prednisone (MP), standard therapy plus thalidomide (MP-T), or the chemotherapy combination VAD (vincristine/doxorubicin [Adriamycin]/dexamethasone) followed by melphalan and transplantation (MEL 100). A total of 447 patients were randomized to one of these 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.
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 greater risk of peripheral neuropathy, neutropenia, and constipation.
"These results are extremely encouraging 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."
Thalidomide Plus Dexamethasone
Another ongoing multicenter, randomized, placebo-controlled phase III study of thalidomide (MM-003) reported at ASCO is comparing oral combination therapy with thalidomide plus dexamethasone vs dexamethasone alone as induction therapy for previously untreated multiple myeloma. In this 470-patient trial, the combination of thalidomide plus dexamethasone led to a statistically significant improvement (P = .0001) in median time to disease progressionthe primary endpointin patients receiving thalidomide plus dexamethasone compared to patients receiving dexamethasone alone. The median overall survival and median time to disease progression have not been reached in the thalidomide-plus-dexamethasone arm of the study.
These data were presented at an oral session during the ASCO meeting, by Vincent Rajkumar, MD, a Mayo Clinic hematologist and oncologist. The median overall survival in patients treated with thalidomide plus dexamethasone has not been reached, compared to 25.2 months with dexamethasone plus placebo (P < .0001). Likewise, the median time to disease progression in patients treated with thalidomide plus dexamethasone has not been reached, compared to 8.1 months with dexamethasone plus placebo.
The best response rate observed with thalidomide plus dexamethasone was 58.5%, compared with 35.3% for dexamethasone plus placebo (P < .01). The complete response rate (based on Blade criteria) with thalidomide plus dexamethasone was 4.7%, compared with 1.3% for dexamethasone plus placebo. The most common side effects observed in this trial with the combination of thalidomide and dexamethasone were constipation, edema, insomnia, fatigue, tremor, and neuropathy.