The addition of lenalidomide to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) did not improve overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) aged 80 years or older, according to results of the phase 3 SENIOR study.1
“Rituximab delivered subcutaneously with miniCHOP remains the gold standard in very elderly patients with DLBCL and led to a 2-year overall survival of 66%,” the study authors wrote.
The study (ClinicalTrials.gov identifier: NCT02128061) included 249 patients with untreated DLBCL (≥80 years). The median patient age was 83 years.
Patients were randomly assigned to receive R-miniCHOP alone or R-miniCHOP plus lenalidomide, which was administered at a dose of 10 mg once daily. The first cycle of rituximab was delivered intravenously; all cycles were administered subcutaneously thereafter. The primary end point was OS.
At a median follow-up of 25.1 months, OS had not improved with the addition of lenalidomide to R-miniCHOP. The 2-year OS was 66.0% with R-miniCHOP compared with 65.7% with R-miniCHOP plus lenalidomide (P =.98). This finding was consistent in both the overall population and the non-GCB population.
In a multivariate analysis, only albuminemia less than 35 g/L was found to be predictive of OS in the overall population and according to treatment arm. Albuminemia, with staging, is recognized as the “most significant factor related to OS, independent of the International Prognostic Index and geriatric scales,” the investigators wrote, adding that it “can be used as a simple and strong prognostic marker.”
The 2-year progression-free survival was 56.2% (95% CI, 46.2-65.1) for R-miniCHOP and 54.8% (95% CI, 44.6-63.9) with the addition of lenalidomide. Grade 3 to 4 adverse events occurred in 53% of patients who received R-miniCHOP and 81% of patients whose regimen included lenalidomide.
“These results may suggest that the treatment regimen proposed in the SENIOR trial was inadequate to deliver a sufficient dose of lenalidomide,” the investigators stated. They added that the toxicity of the R-miniCHOP plus lenalidomide combination could have “strongly affected the final result of the trial.”
“In the SENIOR trial, the very high number of toxicities and comorbidities inherent to this population may lead to negating the beneficial effect of the experimental drug even if the dose intensity of R-miniCHOP received was equivalent in both arms,” they added.
Finally, the negative results could be due to the small number of patients included with the ABC DLBCL subtype, for which lenalidomide therapy is thought to be particularly effective.
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Oberic L, Peyrade F, Puyade M, et al. Subcutaneous rituximab-miniCHOP compared with subcutaneous rituximab-miniCHOP plus lenalidomide in diffuse large B-cell lymphoma for patients age 80 years or older. J Clin Oncol. Published online January 14, 2021. doi:10.1200/JCO.20.02666