Lenalidomide after stem-cell transplantation for multiple myeloma.
Author(s): McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S,
Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile
T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH,
Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E,
Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC,
Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C.
Affiliation(s): Blood and Marrow Transplant Program, Roswell Park Cancer Institute, Buffalo, NY
14263, USA. philip.mccarthy@roswellpark.org
Publication date & source: 2012, N Engl J Med. , 366(19):1770-81
BACKGROUND: Data are lacking on whether lenalidomide maintenance therapy prolongs
the time to disease progression after autologous hematopoietic stem-cell
transplantation in patients with multiple myeloma.
METHODS: Between April 2005 and July 2009, we 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. The
starting dose of lenalidomide was 10 mg per day (range, 5 to 15).
RESULTS: 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. At a median follow-up
of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229
patients who received placebo (58%) had disease progression or had died. 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). More grade 3 or 4
hematologic adverse events and grade 3 nonhematologic adverse events occurred in
patients who received lenalidomide (P<0.001 for both comparisons). Second primary
cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who
received placebo (3%).
CONCLUSIONS: Lenalidomide maintenance therapy, initiated at day 100 after
hematopoietic stem-cell transplantation, was associated with more toxicity and
second cancers but a significantly longer time to disease progression and
significantly improved overall survival among patients with myeloma. (Funded by
the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).
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