Revlimid evaluated as combination oral treatment regimen in newly diagnosed multiple myeloma

07-05-2006

Celgene Corporation (CELG) announced that clinical data from a study with combination therapy lenalidomide (Revlimid), melphalan and prednisone (R-MP) in elderly newly diagnosed multiple myeloma patients show that after seven treatment cycles with R-MP all patients showed a response with no further disease progressions observed, and event-free survival (EFS) (p<0.001) after 9.6 month of follow-up.

Results were reported at an oral presentation during the 42nd American Society of Clinical Oncology (ASCO) Meeting.

Revlimid is now approved by the U.S. Food and Drug Administration (FDA) for treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

"The results from this study are the basis for a pivotal program to be initiated using R-MP in newly diagnosed multiple myeloma later this year," said Jerome B. Zeldis, MD, PhD, chief medical officer of Celgene Corporation.

The trial was designed to evaluate the potential additive and synergistic effects of the combination of R-MP, to define the toxicity profile of R-MP and to analyze the efficacy of this combination in patients with newly diagnosed symptomatic multiple myeloma aged 65 and older. Patients were treated with nine courses of lenalidomide (5-10 mg/day for 21 days every 4-6 weeks) plus MP (melphalan 0.18-0.25 mg/kg and prednisone 2 mg/kg for 4 days every 4-6 weeks).

Four different dose levels were tested: 1) Melphalan 0.18 mg/kg + lenalidomide 5 mg/day; 2) Melphalan 0.25 mg/kg + lenalidomide 5 mg/day; 3) Melphalan 0.18 mg/kg + lenalidomide 10 mg/day; 4) Melphalan 0.25 mg/kg + lenalidomide 10 mg/day. Each cohort included 6 patients.

Dose limiting toxicity (DLT) was defined as any non-hematologic toxicity {{>=}} grade 3 according to NCI toxicity rating scale; grade 4 neutropenia lasting more than 7 days; any other grade 4 hematologic toxicity and any treatment delay due to toxicity that occurred during the first cycle. All patients received ciprofloxacin and aspirin as prophylaxis.

Fifty three patients (median age 71, range 57-77) received at least one R-MP course. No DLTs were observed in the first 2 dose levels. In level 3 one patient experienced DLT (grade 4 neutropenia lasting> 7 days). In level 4 three patients showed DLTs (1 pt experienced neutropenic fever and grade 3 cutaneous toxicity, 1 pt had a pulmonary embolism and delayed cycle 2 due to neutropenia, 1 pt delayed cycle 2 due to hematological toxicity).

After one cycle of R-MP, no one was in complete remission (CR) (according to the EBMT/IBMTR criteria), near complete response (nCR) in myeloma protein reduction of 75-99% was reported in 2.5% of patients, partial response (PR) in myeloma protein reduction of 50-74% was reported in 62.5% of patients and near partial response of less than 50% in myeloma protein reduction was reported in 27.5% of patients;

After seven cycles of R-MP, CR was observed in 17.1% of patients, nCR was observed in 24.4% of patients, PR was observed in 17.1% of patients and nPR was observed in 14.6% of patients; no disease progressions were observed.

Grade 3/4 hematological toxicities included neutropenia (66%), thrombocytopenia (34%) and anemia (17%). Grade 3/4 non-hematological toxicities included cutaneous eruption (10%), infections (5%), and febrile neutropenia (8%).

Revlimid is a member of a proprietary group of novel immunomodulatory compounds, IMiDs. Celgene continues to evaluate Revlimid in a broad range of hematology and oncology conditions. The IMiD pipeline, including Revlimid, is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of-matter and use patents.

Revlimid is approved by the U.S. Food & Drug Administration (FDA) for treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Revlimid is not approved by the FDA or any other regulatory agencies as a treatment for any other indication and is currently being evaluated in clinical trials for efficacy and safety for future regulatory applications.

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.