medwireNews: Lenalidomide maintenance therapy significantly improves progression-free survival (PFS) in elderly patients with diffuse large B-cell lymphoma (DLBCL) who respond to first-line chemotherapy, phase III trial data show.
The REMARC study randomly assigned 650 patients, aged 60 to 80 years, to 24 months of maintenance therapy with the oral immunomodulator lenalidomide 25 mg/day or placebo for 21 of every 28 days. At randomization, the patients all had a complete response (CR) or partial response (PR) to induction therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for previously untreated DLBCL or other aggressive B-cell lymphoma.
As reported in the Journal of Clinical Oncology, patients in the lenalidomide group had a significant 29% reduced risk for disease progression during a median 39 months of follow-up compared with those in the placebo group. The median PFS was not reached in the former group, compared with 58.9 months in the latter.
Catherine Thieblemont (Hôpital Saint-Louis, Paris, France) and study co-authors note that the benefit seen with lenalidomide “was equally important in patients who achieved a CR as in those achieving a PR.”
In addition, the improvement in PFS with lenalidomide did not depend on age, gender, or International Prognostic Index.
A secondary analysis, with a median follow-up of 52 months, showed that overall survival (OS) was not reached in either group, with 2-year estimated OS rates at 87% and 89% for lenalidomide and placebo, respectively. Lymphoma was the leading cause of mortality in both groups, accounting for 59% of deaths among patients receiving lenalidomide and 62% among those receiving placebo.
“At the time of this analysis, we do not yet fully understand the basis for lack of OS benefit despite the positive PFS data, other than that this is not due to excessive toxicity in the experimental arm,” Thieblemont et al remark.
Indeed, their safety data show that serious treatment-emergent adverse events (TEAEs) occurred in 31% of patients receiving lenalidomide and 28% of those receiving placebo, with TEAEs leading to dose reductions reported in 66% and 32%, respectively. Neutropenia and cutaneous reactions were the most common AEs attributed to lenalidomide.
Commenting on their findings, the authors say: “It is unlikely that, in a maintenance setting like REMARC, the clinical benefit observed in the lenalidomide arm could be due to a direct tumoricidal effect- with upregulation of interferon-stimulated genes that require cereblon expression, but rather an immunomodulatory mechanism.”
They add that this suggestion is supported by the fact that PR-to-CR conversion was similar between the lenalidomide and placebo groups, at 33% and 29%, respectively.
Thieblemont and team conclude: “It will be important in REMARC to identify any reliably predictive biomarkers to understand the effect of lenalidomide and better use this drug in routine treatment of aggressive B-cell lymphoma, including DLBCL, [follicular lymphoma grade 3B], and transformed indolent lymphoma.”
By Laura Cowen
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