Maintenance therapy with lenalidomide significantly prolongs progression-free survival (PFS) in elderly patients with diffuse large B-cell lymphoma (DLBCL), according to findings from a phase III trial.

None of the previous trials assessing a maintenance drug in this patient population – including bevacizumab, rituximab, enzastaurin, or everolimus – have reported such a benefit, Catherine Thieblemont, MD, PhD, of the department of hematology-oncology, Hôpital Saint-Louis, Paris, and her associates, reported.

The standard regimen for newly diagnosed DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but 30%-40% of patients have disease progression or relapse, usually during the first 2 years after diagnosis. Lenalidomide is an immunomodulator with antineoplastic activity and has shown activity in relapsed DLBCL. The investigators compared 24 months of lenalidomide maintenance therapy against a matching placebo in an international, randomized double-blind phase III trial involving 650 patients aged 60-80 years who showed either partial or complete responses to first-line R-CHOP.

After a median follow-up of 39 months (range, 0-74 months), median PFS was not yet reached in the lenalidomide group and was estimated to be 58.9 months in the placebo group, for a hazard ratio of 0.708 favoring lenalidomide. This represents a statistically significant and clinically meaningful improvement in PFS, Dr. Thieblemont and her associates noted (J Clin Oncol. 2017 Apr 20. doi: 10.1200/JCO.2017.72.6984 ).

This survival benefit was consistent across all subgroups of patients. Most important, PFS was significantly prolonged regardless of whether patients had shown only a partial response or a complete response to R-CHOP, the investigators said.

The maintenance therapy did not appear to prolong overall survival, which was 87% for lenalidomide and 89% for placebo.

“We do not yet fully understand the basis for lack of an [overall survival] benefit despite the positive PFS data. Other than that, this is not due to excessive toxicity in the experimental arm,” they said. “We speculate the reason may be differences in the outcomes after progression or some other unrecognized reason.”

The study was sponsored by the Lymphoma Academic Research Organisation of France and Celgene. Dr. Thieblemont reported ties to Celgene, Bayer, AbbVie, Janssen, and Roche. Her associates reported ties to numerous industry sources.