For the first time, a study shows that using an immunomodulatory agent as maintenance therapy prolongs progression-free survival for patients with diffuse large B-cell lymphoma after first-line treatment with rituximab plus CHOP.
SAN DIEGO-For the first time, a study shows that using an immunomodulatory agent as maintenance therapy prolongs progression-free survival (PFS) for patients with diffuse large B-cell lymphoma (DLBCL) after first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), according to a presentation (abstract 471) at the American Society of Hematology 58th Annual Meeting and Exposition, held December 3–6.
R-CHOP is the standard first-line treatment for elderly patients with DLBCL; however, 30% of patients will relapse and 70% of relapsed patients will die within 2 years of diagnosis, said lead author Catherine Thieblemont, MD, PhD, of Hospital Saint-Louis in Paris, France.
She presented the results of the REMARC study, an international, multicenter, double-blind, randomized, placebo-controlled, phase III trial designed to assess the benefit of lenalidomide maintenance after response to R-CHOP in patients aged 60 to 80 years with untreated DLBCL, FL3b or transformed lymphoma.
Patients achieving a complete response (CR) or partial response (PR) at the end of 6 or 8 cycles of R-CHOP21 or R-CHOP14 were stratified by response status and randomized to receive 2 years of lenalidomide maintenance 25 mg per day for 21 of every 28 days or placebo. The primary endpoint was PFS. Secondary endpoints were safety, PR to CR conversion rate, and overall survival.
At the end of R-CHOP therapy, 650 patients, median age 68 years, were randomized to maintenance, either in CR (495 patients) or in PR (152 patients); 323 patients received lenalidomide and 327 patients received placebo. Almost all of the patients had DLBCL.
At a median follow-up of 40 months, median PFS was not reached for the lenalidomide group and was 58.8 months for the placebo group. “The statistically significant benefit in PFS favored lenalidomide. The 1.4-times longer PFS translates into 24 months of projected improvement with lenalidomide,” said Thieblemont, who added that the improvement in PFS was shown in all subgroups analyzed.
An analysis of the cell of origin showed no difference in PFS in patients with activated Bâcell like (ABC), germinal center Bâcell like (GCB), or unclassified profile.
With maintenance, about 20% of patients in both arms converted from PR to CR with a median time to conversion of about 6 months.
At a median follow-up of 52 months, there was no statistically significant difference in overall survival between the two arms. A multivariate analysis showed that treatment arm was not a statically significant factor, she said.
Treatment exposure was similar in both groups in terms of median average daily dose. Lenalidomide patients received fewer median number of maintenance cycles (15) compared to placebo (25). There were more dose reductions due to toxicity and twice as many discontinuations due to toxicity in the lenalidomide arm than the placebo arm.
Grade 3/4 neutropenia was more than twice as frequent with lenalidomide (56%) than with placebo (22%). The number of secondary primary malignancies was similar.
In conclusion, Thieblemont said the study “achieved its primary endpoint of a statistically significant and clinically meaningful improvement in PFS for patients receiving lenalidomide. At a median follow-up of 52 months, the analysis of overall survival, a key secondary endpoint, showed no difference between the lenalidomide and placebo arms.”