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A Randomized Study of Lenalidomide with High- or Low-Dose Dexamethasone in the Treatment of Newly Diagnosed Myeloma
By S. Vincent Rajkumar, MD

Dr. Rajkumar presented data on a large, randomized Phase III trial that compared Revlimid + high-dose dexamethasone (40 mg 4-day pulse) vs. Revlimid + low-dose dexamethasone (40 mg once per week). Interim results indicate increased toxicities with the high-dose dex, especially in the rate of deep vein thrombosis: 18-20% for high-dose dex vs. 5-6% with low-dose dex. Efficacy data will be ready for presentation next year.


A Randomized Phase III Trial of Lenalidomide Plus High-Dose Dexamethasone Versus Lenalidomide Plus Low-Dose Dexamethasone in Newly Diagnosed Multiple Myeloma (E4A03): A Trial Coordinated by the Eastern Cooperative Oncology Group. Session Type: Oral Session

S. Vincent Rajkumar, Susanna Jacobus, Natalie Callander, Rafael Fonseca, David Vesole, Philip Greipp Hematology, Mayo Clinic, Rochester, MN; Dana Farber Cancer Institute, Boston, MA; University of Wisconsin, Madison, WI; Mayo Clinic Arizona, Scottsdale, AZ; St. Vincents Hospital, New York, NY

Background: Lenalidomide has shown efficacy in patients with relapsed myeloma in phase II and III clinical trials, and is currently being investigated as initial therapy for the disease. We report results of a phase III trial comparing lenalidomide plus high-dose dexamethasone (Dex) versus lenalidomide plus low-dose Dex as first line therapy in newly diagnosed multiple myeloma (MM). Methods: Pts with newly diagnosed, untreated, symptomatic MM were eligible. Pts in both arms received lenalidomide 25 mg/day PO on days 1-21 every 28 days. In addition, patients in the high-dose Dex arm (Arm A) received Dex 40 mg on days 1-4, 9-12, and 17-20 PO every 28 days, while pts in the low-dose Dex arm (Arm B) received Dex 40 mg on days 1, 8, 15, and 22 PO every 28 days. The primary endpoint was best response at 4 months on intent to treat basis. At 4 months pts could go off study for stem cell transplant or elect to continue therapy until progression. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or higher. If the serum M protein was unmeasurable, a 90% or higher decrease in urine M protein was required. Responses need to be confirmed at least 4 weeks apart. Patients with disease progression or not responding to lenalidomide within 4 months switched to thalidomide with the same dose of dexamethasone they were receiving (Arms C and D, respectively). An independent Data Monitoring Committee approved release of these results. Results: 445 pts were enrolled: 223 randomized to Arm A and 222 to Arm B. Median age was 65 yrs. Serious adverse event data based on expedited reporting (AdEERS) is available on all pts (see table). Common adverse events of Grade 3 or higher were thromboembolism (18.4% in arm A vs 5.4% in Arm B), infection/pneumonia (18.8% vs 9.0%) and hyperglycemia (5.8% vs 1.8%). Incidence of any grade 4 or higher toxicity was 22.0% in Arm A vs 12.6% in Arm B. Response data is being analyzed. Conclusions: Lenalidomide plus two different schedules of Dex was investigated in this phase III trial. Preliminary results suggest that toxicity rates are higher in the high-dose Dex arm. The differences in the response rates between the two arms will dictate future trials and clinical practice.

Major Toxicties (AdEERS)
Toxicity Arm A (n=223) Arm B (n=222)
Cardiac ischemia (Grade >=3) 2.7% 0.5%
Hyperglycemia (Grade >=3) 5.8% 1.8%
Infection/Pneumonitis (Grade >=3) 18.8% 9.0%
Neuropathy (Grade >=3) 0.9% 0.9%
Thromboembolism (Grade >=3) 18.4% 5.4%
Any non-Hem toxicity (Grade >=3) 53.4% 36.0%
Any toxicity (Grade >=4) 22.0% 12.6%
Death (Grade 5) 4.5% 1.4%

Abstract #799 appears in Blood, Volume 108, issue 11, November 16, 2006

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