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Lenalidomide used continuously after autologous hematopoietic stem cell transplantation significantly prolonged the time to disease progression and overall survival in patients with multiple myeloma.
Philip L. McCarthy, MD
The immunomodulator lenalidomide used continuously after autologous hematopoietic stem cell transplantation significantly prolonged the time to disease progression and overall survival in patients with multiple myeloma compared with placebo, according to the results of the phase III CALGB 100104 study.
Maintenance lenalidomide is, however, associated with increased toxicity and second primary cancers.
“This study suggests that lenalidomide maintenance therapy until disease progression is feasible for long-term use,” Philip L. McCarthy, MD, director of the Blood and Marrow Transplant Program at Roswell Park Cancer Institute in Buffalo, New York, and his co-authors wrote.
Investigators at 47 centers randomized 460 patients with stable disease or a marginal, partial, or complete response 100 days after undergoing a single stem-cell transplantation to maintenance lenalidomide (10 mg daily) or placebo until disease progression.
Multiple myeloma is largely incurable, and disease relapse/progression is the primary cause of treatment failure after high-dose autologous stem cell transplantation, the authors noted. Maintenance of a prolonged progression-free interval with minimal toxicity is an important objective in managing this disease.
The primary endpoint was time to disease progression, defined as time to progressive disease or death from any cause after transplantation.
The study was unblinded in 2009, after a median follow-up of 18 months, when 47 of 231 lenalidomide-treated patients (20%) had progressive disease or had died versus 101 of 229 placebo-treated patients (44%; P <.001). Of the remaining 128 patients who received placebo and did not have progressive disease, 86 crossed over to lenalidomide.
At a median follow-up of 34 months, 86 of 231 lenalidomide-treated patients (37%) and 132 of 229 placebo-treated patients (58%) had disease progression or had died. The median time to progression was 46 months and 27 months in the lenalidomide and placebo groups, respectively (P <.001). Overall, 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P = .03).
The lenalidomide group had a higher rate of grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events (P <.001 for both comparisons).
Of the 231 lenalidomide-treated patients, 8 (3.5%) developed new hematologic cancers and 10 (4.3%) developed solid-tumor cancers. Of the 229 placebo-treated patients, 1 (0.4%) developed new hematologic cancer and 5 (2.2%) developed solid-tumor cancers. The increase in second primary solid-tumor cancers in patients treated with the immunomodulator was not associated with a specific tumor type, and potential causes for the increase have not been clarified, the authors pointed out. They recommended close monitoring of blood counts and standard screening for cancers.
Finally, they said that future research is needed to determine whether combining other new agents with lenalidomide will further extend the time to disease progression and overall survival.
McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1770-1781.