Continuous therapy with Celgene's Revlimid prolongs PFS in older patients with newly diagnosed multiple myeloma
Thursday, May 10 2012 | Comments
Treatment with melphalan hydrochloride, prednisone and Celgene Corp.
's Revlimid (lenalidomide) followed by Revlimid maintenance therapy (MPR-R) significantly prolongs progression-free survival (PFS) among older patients with newly diagnosed multiple myeloma who are ineligible for transplantation, particularly in those aged 65 to 75 years, according to research published in the May 10 issue of The New England Journal of Medicine
During the study, which was funded by Celgene, 459 patients aged 65 years or older were randomized to receive one of three treatments: MPR-R, melphalan, prednisone and Revlimid followed by placebo maintenance therapy (MPR) or melphalan, prednisone and placebo with placebo maintenance therapy (MP).
The MPR-R regimen consisted of induction with nine 28-day cycles of melphalan, prednisone and Revlimid, followed by Revlimid maintenance until disease progression or the development of unacceptable rates of adverse effects. The MPR and MP groups received similar induction with or without Revlimid, accordingly, followed by placebo maintenance. All patients received aspirin thromboprophylaxis during induction.
PFS was the main endpoint of the study, which had a median follow-up of 30 months.
Among the patients who received MPR-R, median PFS was 31 months, which was significantly longer than the median PFS with MPR (14 months) or MP (13 months).
Further, the patients who were treated with MPR-R and MPR had superior response rates in comparison with those who received MP (77 percent and 68 percent, respectively, vs. 50 percent).
The PFS benefit associated with MPR-R was evident in patients aged 65 to 75 years but less so in those aged older than 75 years. In the younger of the two subpopulations, MPR-R significantly prolonged PFS as compared with MPR and MP (median, 31 months vs. 15 months and 12 months, respectively). In the older group, median PFS was 19 months, 12 months and 15 months for the MPR-R, MPR and MP treatment arms, respectively.
The three-year overall survival rate, a secondary endpoint, was 70 percent with MPR-R, 62 percent with MPR and 66 percent with MP, reflecting nonsignificant between-group differences, while the mortality rate was 28 percent for the MPR-R group, 34 percent for the MPR group and 29 percent for the MP group.
The most frequently reported adverse events during induction therapy were hematologic; grade IV neutropenia was reported in 35 percent, 32 percent and 8 percent of the patients in the MPR-R, MPR and MP treatment arms, respectively.
Revlimid is approved for use in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one previous therapy. It is also approved for the treatment of patients with transfusion-dependent anemia resulting from low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities.
Earlier this month, the Food and Drug Administration
issued an updated drug safety communication to alert patients and health care professionals of an increased risk of second primary malignancies (i.e., new types of cancer) among certain patients who receive treatment with Revlimid.
Specifically, the FDA noted that trials conducted after Revlimid's approval showed that patients with newly diagnosed multiple myeloma who were treated with Revlimid had an increased risk of developing acute myelogenous leukemia, myelodysplastic syndromes and Hodgkin's lymphoma as compared with patients who received placebo. The drug's label and patient medication guide have been updated to include this new information.
This information concerns a use that has not been approved by the FDA.