By Bruce Sylvester
VIENNA, AUSTRIA -- June 11, 2007 -- For elderly patients who are newly diagnosed with multiple myeloma, addition of lenalidomide to a standard oral melphalan and prednisone regimen significantly increases both the response rate and the event-free survival rate.
"We saw a 53% response rate after 1 course of the triple combination therapy compared with 48% response rate after 6 courses of melphalan and prednisone," said presenter and investigator Antonio Palumbo, MD, professor of medicine, University of Torino, Torino, Italy. "This has clear implications for avoiding adverse events from extended treatment in this elderly population."
The findings were reported in an oral session here on June 9th at the 12th Congress of the European Hematology Society (EHA).
The open-label trial was designed to evaluate dosing, safety, and efficacy of melphalan/prednisone plus lenalidomide (MPR) in newly diagnosed symptomatic elderly patients diagnosed with multiple myeloma. The primary endpoints of the trial were identification of the maximum tolerated dose and determination of response rate. Secondary endpoints were rates of event-free survival and overall survival.
The investigators enrolled 54 subjects with a median age of 71 years (range 57-77). Each subject received 9 cycles of lenalidomide 5 to 10 mg/day for 21 days plus melphalan 0.18 to 0.25 mg/kg for 4 days and prednisone 2 mg/kg for 4 days every 4 to 6 weeks, followed by maintenance therapy with lenalidomide monotherapy 10 mg/day for 21 days every month.
Subjects took aspirin 100 mg/day as antithrombotic prophylaxis.
The researchers tested 4 dosing levels. They reported that the maximum tolerated dose was lenalidomide 10 mg/day for 21 days and melphalan 0.18 mg/kg for 4 days every 4 to 6 weeks.
After reaching the maximum tolerated dose and after 1 year, the investigators saw partial responses in 81% of the subjects, including 47.6% that had at least a very good partial remission and 23.8% that showed immunofixation-negative complete responses.
One-year event-free survival and overall survival rates were 92% and 100%, respectively.
Dr. Palumbo noted that, at a median follow-up of 21.8 months, the event-free survival rate for the triple therapy was 95%.
The investigators also reported the following major grade 3/4 adverse events: haematological toxicities (69.8%), nonhaematological grade 3/4 febrile neutropenia (9.4%), cutaneous rash (7.5%), and thromboembolism (5.7%). Two of the 3 thromboembolic events happened following discontinuation of aspirin prophylaxis.
"This trial shows a very high response rate and no early death," concluded Dr. Palumbo. "The clinical implications for elderly patients are evident and will be evaluated in further studies."
"[Lenalidomide] is changing the paradigm for multiple myeloma treatment overall," commented Brian Durie, MD, haematologist/oncologist and senior advisor for haematological malignancies, Cedars-Sinai Hospital, Los Angeles, California, United States. "It is an oral treatment that is producing fantastic results."
Lenalidomide in combination with dexamethasone is currently approved by the United States Food and Drug Administration (FDA) for the treatment of multiple myeloma in patients who have received at least 1 prior therapy. It is also FDA-approved for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1–risk myelodysplastic syndromes associated with a deletion 5q (deletion of chromosome 5q) cytogenetic abnormality with or without additional cytogenetic abnormalities.
The study was supported by Celgene Corporation, which markets lenalidomide under the trade name Revlimid®.
[Presentation title: Oral Melphalan, Prednisone and Lenalidomide for Elderly Newly Diagnosed Myeloma Patients. Abstract 402]
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