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| |  ASH: Thalomid (Thalidomide) Promising In Treating Refractory Multiple Myeloma SAN FRANCISCO, CA -- December 5, 2000 -- Researchers from the Arkansas Cancer Research Center, Mayo Clinic, and M.D. Anderson Cancer Center presented data at the 42nd annual meeting of the American Society of Hematology on clinical trials evaluating the safety and efficacy of Thalomid (thalidomide) as a single agent and in combination treatment for multiple myeloma. Studies presented included new clinical trial data on the use of Thalomid alone and Thalomid in combination with conventional therapies for treatment of patients with early stage multiple myeloma. In addition, clinical data presented was consistent with previously published results on the potential use of Thalomid in treating refractory multiple myeloma and included survival data of patients. "The new data presented at this meeting greatly expands our knowledge base on Thalomid's potential role in treating multiple myeloma both as a single agent and in combination with a range of chemotherapeutic agents. For the first time, results of clinical trials studying newly diagnosed myeloma patients with Thalomid in combination with other agents were discussed," said Sol J. Barer, Ph.D., President and COO of Celgene Corporation. "We will continue to expand our clinical trial programs for Thalomid, intended to lead to a supplemental New Drug Application to the FDA in 2001." Researchers from the Mayo Clinic led by S. V. Rajkumar, M.D., presented an interim analysis of an ongoing trial using thalidomide alone or in combination with dexamethasone for treatment of newly diagnosed patients with multiple myeloma. Forty-two (26 with active disease, 16 with smoldering/indolent disease) patients were randomized to receive a starting thalidomide dose of 200 mg/day escalated by 200 mg every two weeks according to tolerance to a maximum 800 mg/day alone or with 40mg/day of oral dexamethasone. Seventy-seven percent of patients with active disease achieved response (greater than or equal to 50 percent reduction in serum and/or urine monoclonal protein (M-protein)). Eighty-six percent of patients who received thalidomide dose escalation and 74 percent of patients with the constant thalidomide dose in combination with dexamethasone achieved response. For patients receiving thalidomide alone, 38 percent experienced a response. Due to grade 3-4 skin toxicity in two patients among the first seven patients in the thalidomide plus dexamethasone treatment arm, the dose escalation of thalidomide was stopped and all patients continued receiving 200 mg/day of thalidomide alone or in combination with dexamethasone. Major side effects observed include rash in three patients, sedation, constipation and myalgias in one patient each. "Based on these encouraging interim results, thalidomide, in combination with dexamethasone, may be an active first-line treatment for patients newly diagnosed with active multiple myeloma," says Dr. Rajkumar. "Although further study and analysis is needed to confirm these preliminary results, these data suggest that there may be a potential use for this combination in treating patients with myeloma." Bart Barlogie, M.D., Ph.D., Director of the Arkansas Cancer Research Center, presented results on long-term follow-up of 169 patients enrolled in a dose escalation trial evaluating the potential use of thalidomide (starting dose 200 mg/day escalated by 200 mg every two weeks according to tolerance to a maximum 800 mg/day) as a single agent for refractory multiple myeloma. According to the data presented, 36 percent of patients achieved at least 25 percent reduction in M-protein. Reductions in paraproteins were associated with corresponding reduction in bone marrow plasmacytosis, recovery from anemia/thrombocytopenia and uninvolved immunoglobulins. Twenty-four patients remain on study; the main reasons for discontinuing therapy include disease progression in 98 patients (22 deaths) and toxicity in 28 patients (4 deaths). With a median follow-up of 22 months among 84 alive patients, 48 +/- 6 percent are projected alive at 2 years and 20 +/- 6 percent are projected event-free. For perspective, Dr. Barlogie also outlined an eight month landmark analysis (when more than 90 percent of patients had achieved more than 25 percent M-protein reduction) was conducted among 124 surviving patients. At 18 months, 78 percent of 56 responding patients (25 percent reduction) survived compared to 53 percent among the remaining 68 non-responders (p= 0. 02). For this high-risk patient group at 18 months, there is a 55 percent overall patient survival rate with 30 percent event free survival, and durable response in 26 percent. Major side effects seen were sedation, confusion, depression, tremor, constipation, weakness and sensory neuropathy, somnolence and tingling/numbness in ten percent of patients who received a 400 mg dose of thalidomide. "Our results suggest that thalidomide may have single agent activity in advanced and refractory high risk multiple myeloma," says Dr. Barlogie. "These results are consistent with our earlier observations that thalidomide may improve patient survival in this very difficult disease." The data presented suggest that direct anti-tumor activity of thalidomide on human multiple myeloma cells may result in positive responses when used alone or in combination therapy for patients with advanced disease. In addition, the data suggest that thalidomide may act synergistically with other anti-myeloma agents. Twenty-one additional abstracts studying thalidomide in the setting of multiple myeloma were presented, including results on thalidomide in combination with conventional therapies for relapsed or refractory multiple myeloma. There were additional abstracts presented at this meeting studying the potential use of thalidomide in myelodysplastic syndromes, Castleman's disease and acute myeloid myeloma. There are approximately 40,000 people in the United States living with multiple myeloma and 13,000 new cases of multiple myeloma are diagnosed each year in the United States, making it the second most common blood cancer. Incurable with conventional chemotherapy, multiple myeloma is a malignant cancer of the plasma cells, which are a type of white blood cell found in many tissues of the body, but mainly in the bone marrow. As the cancer grows it destroys normal bone tissue, causing pain and crowding out normal blood cell production. There are nearly 11,000 deaths expected during 2000, according to the Multiple Myeloma Research Foundation. Thalidomide is contraindicated in pregnant women and women capable of becoming pregnant. Even a single capsule taken by a pregnant woman can cause severe birth defects or death to an unborn baby. To minimize this risk, only prescribers and pharmacies registered with the System for Thalidomide Education and Prescribing Safety (S.T.E.P.STM) distribution program may prescribe or dispense Thalomid® (thalidomide). Other adverse drug reactions known to be associated with thalidomide therapy include: peripheral neuropathy, a common, potentially severe side effect that may be irreversible; drowsiness/somnolence; dizziness/orthostatic hypotension; neutropenia; hypersensitivity reactions; and increased HIV-viral load. Physicians should consult full prescribing information about these and other adverse reactions prior to initiating treatment with Thalomid(R). Thalomid (thalidomide), manufactured by Celgene Corporation, received U.S. Food and Drug Administration (FDA) clearance on July 16, 1998 for the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and as maintenance therapy for prevention and suppression of cutaneous manifestation recurrences. Thalomid is not indicated as monotherapy for ENL treatment in the presence of moderate to severe neuritis. Related Link: Thalomid (thalidomide).
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