Today, high-dose therapy with autologous stem cell transplantation (ASCT) is a standard treatment for myeloma patients. But a residual disease (RD) responsible for relapse is always present. As a result, effective maintenance treatment is required. However, such treatment is still to be defined.

Researchers have found that thalidomide reduced RD. Neuropathy is, however, one of the major limiting factors of thalidomide. Lenalidomide, a thalidomide analog devoid of neurological toxicity, has been investigates as an alternative.

Results from an interim analysis of a Phase III trial show that maintenance therapy with lenalidomide (Revlimid) slowed disease progression by 54% among patients with multiple myeloma who had prior high-dose chemotherapy and an autologous stem cell transplant. Maintenance therapy is longerterm treatment given after patients achieve remission with initial therapy, with the goal of prolonging remission.

“These results are very promising. If confirmed in the final analysis, they suggest that maintenance therapy with lenalidomide can improve quality of life in patients with myeloma by delaying the need for more intensive therapy to treat a relapse,” said Michel Attal, PhD, professor of hematology at Purpan Hospital in Toulouse, France and the lead author of the study, which was conducted by the French-Speaking Intergroup for Myeloma (Intergroup Francophone du Myelome). Final data on progression-free survival and overall survival are expected to be reported in December 2010.

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Multiple myeloma, a cancer of the bone marrow, is treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) – a procedure in which some of a patient’s stem cells are removed before therapy and returned after treatment to rebuild the patient’s immune system. Despite this aggressive approach, however, more than 90% of patients eventually experience a cancer relapse.

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Prior research has shown that maintenance therapy with the chemically similar drug thalidomide can delay myeloma relapse, but this drug has significant toxic effects on the nervous system and was only effective in a limited group of patients.

Lenalidomide is an oral drug that is already used to treat myeloma that recurs or persists despite prior therapy. In this study, investigators compared the time it took for a patient’s myeloma to progress (Progression-free Survival; PFS) between 307 patients who were randomly assigned to receive maintenance lenalidomide until relapse and 307 patients who received a placebo.

Patient?s characteristics of each group were similar and no significant differences were found with regard to age (57 years), ISS stage, FISH analysis, induction regimen (VAD/bortezomibdex/thalidomide-dex/others=49%/44%/3%/2%), diagnosis-randomization interval (10 months), and response at time of randomization. All patients with non-progressive disease had previous treatment with high-dose therapy and ASCT within six months of randomization, followed by two months of lenalidomide “consolidation” therapy (25 mg/d, 21 days/month, for 2 months) followed by a maintenance with either lenalidomide (10 to 15 mg/d) until relapse (Arm A) or placebo (Arm B). Lenalidomide treatment after initial therapy to achieve a complete remission; consolidation therapy uses a higher dose of lenalidomide than maintenance therapy.

Lenalidomide maintenance therapy improved three-year progression-free survival: 68% of patients in the lenalidomide group did not experience disease progression, compared with 35% of the placebo group. This benefit was observed whether or not patients had achieved a complete response after ASCT.

In multivariate analysis, PFS was related to response after consolidation, beta-2 microglobulin at diagnosis, and treatment arm. A strong interaction (p<0.04) was found between the efficacy of arm B and beta 2-microglobulin (HR=0.3, p <10-4 for beta-2 m <=3 mg/l; HR=0.58, p<0.003 for beta-2 m > 3 mg/l).

Two-year overall survival was similar in both groups (95%). Maintenance lenalidomide was well tolerated. These results show that lenalidomide is an effective maintenance treatment which prolongs (PFS) after ASCT.

Oral Abstract Session: Myeloma
Lead author:Michel Attal, PhD, Purpan Hospital, Toulouse, France
Date:Sunday, June 6, 2010, 11:15-11:30 AM CDT, Room E354b
Abstract: 8018
Title:Lenalidomide maintenance after transplantation for myeloma.
Authors: M. Attal, C. Cristini, G. Marit, D. Caillot, T. Facon, C. Hullin, P. Moreau, C. Mathiot, H. Avet-Loiseau, J. L. Harousseau, Intergroupe Francophone du Myelome.

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