A phase 3 study has demonstrated that maintenance therapy with the oral drug lenalidomide (Revlimid) is associated with significantly improved progression-free and overall survival in patients with newly diagnosed myeloma who have undergone autologous hematopoietic stem-cell transplantation.
“The results of this trial will change our treatment of multiple myeloma patients,” predicted Thomas Shea, MD, director of the Bone Marrow and Stem Cell Transplant Program at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, in a statement announcing his group’s findings.
Lenalidomide is an immunomodulatory agent that helps bone marrow produce normal blood cells and kills abnormal cells in the bone marrow. As Shea and colleagues explained in their report for The New England Journal of Medicine (2012;366:1770-1781), data had been lacking as to whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous stem cell transplant in persons with multiple myeloma. The investigators randomized 460 patients younger than age 71 years to lenalidomide (starting dose: 10 mg/day; range: 5 mg/day to 15 mg/day) or placebo, which was administered until disease progression. At the start of the study each patient had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation.
The study began in April 2005 and was unblinded in July 2009, when a planned interim analysis showed a significantly longer time to disease progression for the lenalidomide users. At unblinding, 20% of the lenalidomide patients had progressive disease or had died, compared to 44% in the placebo group. At a median follow-up of 34 months, 86 of 231 patients (37%) who received lenalidomide and 132 of 229 patients (58%) who received placebo had disease progression or had died. The median time to progression was 46 months for lenalidomide users and 27 months for placebo users.
Lenalidomide was associated with more toxicity and second cancers than was placebo. A total of 35 patients receiving lenalidomide (15%) died, compared with 53 (23%) of placebo users. More grade 3 or 4 hematologic adverse events and more grade 3 nonhematologic adverse events occurred among the lenalidomide users. Second primary cancers developed in 18 lenalidomide users (8%) and in six placebo users (3%).
Despite these results, Shea noted, lenalidomide generally appears to be well-tolerated when given long-term.