In a phase III trial of patients age 80 or older with diffuse large B-cell lymphoma (DLBCL), attempts to improve on the standard approach of rituximab plus an attenuated dose of chemotherapy (R-miniCHOP; cyclophosphamide, doxorubicin, vincristine, prednisone) by adding lenalidomide were unsuccessful. However, the authors were able to find risk factors that identified patients who would have poorer overall survival (OS), independent of the International Prognostic Index (IPI) or other scoring systems.
The findings were published in the Journal of Clinical Oncology by Lucie Oberic, MD, from the Institut Universitaire du Cancer of Toulouse-Oncopole in France.
“To the best of our knowledge, [the SENIOR trial is] the first randomized phase III study dedicated to patients with DLBCL … over [age] 80,” the authors wrote. “In this challenging setting, we have proven that a larger prospective study is possible.”
The SENIOR trial randomized 249 older patients with untreated DLBCL to receive either:
- R-miniCHOP (n=127)
- lenalidomide plus R-miniCHOP (R2-miniCHOP; n=122)
Following a pre-phase treatment of vincristine and prednisone, treatment was administered in 21-day cycles for six cycles. In the R2-miniCHOP group, lenalidomide was given at a dose of 10 mg once daily on days one to 14 every three weeks.
The median age across the entire population was 83 years (range = 80-96). Of patients who were classified according to immunohistochemistry, 45% had a germinal center B-cell–like subtype (40% in the R-miniCHOP group and 50% in the R2-miniCHOP group).
During just over 25 months of follow-up, approximately 80% and 86% of patients received all six planned cycles of R-miniCHOP and R2-miniCHOP arms, respectively. In the R2-miniCHOP group, 20 patients (17%) required a lenalidomide dose reduction; the majority of these instances (n=17; 85%) were due to adverse events (AEs).
Overall, the primary endpoint of OS was not significantly different between the two treatment arms, with a 2-year OS of 66% in the R-miniCHOP group and 65.7% in the R2-miniCHOP group (hazard ratio [HR] = 0.99; p=0.98).
Rates of two-year progression-free survival were also similar with each regimen: 56.2% and 54.8% (HR=1.027; p=0.89). There also were no significant differences in survival when looking specifically at DLBCL subtype, the investigators added.
“In this trial, we failed to reject the null hypothesis,” the researchers reported, offering several potential explanations. “The proposed treatment regimen might not be adequate and brings insufficient doses of lenalidomide to the patient,” they wrote. “In this category of very elderly patients the dose of 10 mg once daily [on days 1-14, or 140 mg/cycle] has been proposed and is accompanied by significant additional toxicity, suggesting that a higher dose would probably not have been properly tolerated.”
In the safety population, which included 241 participants, 70% of those who received R-miniCHOP and 86% of those who received additional lenalidomide experienced an AE. Lenalidomide treatment also was associated with a higher incidence of grade 3/4 AEs (83%) compared with R-miniCHOP (74%). The most common grade 3-4 AEs included neutropenia (18% with R-miniCHOP and 35% with R2-miniCHOP), infections (8% and 13.5%), and anemia (5% and 9%).
When the researchers conducted a multivariate analysis to detect factors that could predict clinical outcome, they identified albuminemia <35 g/L as the only component predictive of OS. Identification of these potential factors “makes it possible to identify the most fragile patients for whom standard chemotherapy based on immunochemotherapy does not seem to be adequate, even after a pre-phase has been performed in all patients,” they concluded. Along with staging, albuminemia is the most significant factor, independent of the IPI, MNA score, or IADL scale.
However, the researchers cautioned that “the very high number of toxicities and comorbidities inherent to this population may lead to negating the beneficial effect of this experimental drug even if the dose intensity of R-miniCHOP received was equivalent in both arms.”
Study authors report relationships with Celgene and Roche, which supported this trial.
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. 2021 January 14. [Epub ahead of print]