New studies show benefit of lenalidomide maintenance therapy in multiple myeloma
Lenalidomide maintenance after autologous hematopoietic stem-cell transplantation
- Date : 22 May 2012
- Topic : Haematologic malignancies
Studies published in the New England Journal of Medicine offer promising news about a new long-term therapy, lenalidomide, that can be used after autologous hematopoietic stem-cell transplantation to slow down the progression of multiple myeloma.
Multiple myeloma is a form of malignancy where the plasma cells in the bone marrow grow out of control, causing bone fractures as well as predisposing patients to anaemia, infection and renal failure. An autologous hematopoietic stem cell transplantation is frequently an important treatment option for many patients. Unfortunately, multiple myeloma continues to progress even after the transplantation.
The results of phase III lenalidomide maintenance studies
Between April 2005 and July 2009, the researchers from several USA institutions randomly assigned 460 patients, who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. This clinical trial measured the effect of maintenance lenalidomide therapy on disease-free progression after transplantation.
This phase III study demonstrated that maintenance therapy with lenalidomide, an oral drug that can be taken for many months or even years, is associated with significant improvement in outcomes for patients with newly diagnosed myeloma who have undergone the transplantation.
The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (p < 0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide.
The probability of surviving free of disease progression (the primary end point) for three years was 58% in the lenalidomide group, as compared with 37% in the placebo group. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (p < 0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (p = 0.03).
Prolonged treatment with lenalidomide generally well tolerated
More grade 3 or 4 haematologic adverse events and grade 3 non-haematologic adverse events occurred in patients who received lenalidomide. Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%).
While lenalidomide has some risks, including an increase in people developing second cancers, it generally appears to be well-tolerated when given long-term and was associated with a delay in time to progression of the myeloma as well as an improvement in overall survival.
Another phase III study in France randomly assigned 614 patients younger than 65 years of age who had non-progressive disease after first-line transplantation to maintenance treatment with either lenalidomide or placebo until relapse. The results showed similar improvement in delaying progression of the myeloma following transplantation, but did not improve overall survival after transplantation compared to those receiving a placebo.
Additional studies need to be conducted and longer follow-up of the current studies will need to be undertaken to confirm whether there is a real survival benefit of lenalidomide therapy for these patients.
The USA trial was supported by the National Cancer Institute. Celgene provided the lenalidomide and placebo used in the trial.
The French study was supported by the Programme Hospitalier de Recherche Clinique, the Swiss Group for Clinical Cancer Research (SAKK), and a grant from Celgene. Celgene provided the lenalidomide and placebo used in the trial.
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