Martin Trněny, MD
The combination of lenalidomide (Revlimid) and rituximab (R2
) showed a 34% reduction in the risk of disease progression or death compared with rituximab plus placebo in patients ≥70 years old with indolent non-Hodgkin lymphoma, although it was not found to be statistically significant, according to findings of a subgroup analysis of the phase III AUGMENT trial presented at the 2019 ASH Annual Meeting.1
However, the PFS benefit was more pronounced in patients with follicular lymphoma and were ≥70 years old (HR, 0.49; 95% CI, 0.25-0.99; P
= .043). Additionally, the safety profiles of the regimen were similar to that of the overall study population of patients with indolent NHL.
“These data show that R2
maintained efficacy improvements versus rituximab/placebo in patients aged ≥70 years, despite higher unfit status and lower overall lenalidomide treatment and exposure compared with the overall population,” lead study author Martin Trněny, MD, professor of medical oncology, director of Stem Cell Transplantation Program and Lymphoma Program at General Hospital, Charles University Prague, said in a presentation during the meeting. “R2
is an effective and available treatment option for patients with indolent NHL, including those with advanced age.”
In May 2019, the FDA approved the R2
regimen for use in patients with previously treated follicular lymphoma and marginal zone lymphoma (MZL). The decision was primarily based on results of the phase III AUGMENT study, in which the combination reduced the risk of disease progression or death by 54% versus rituximab alone in patients with relapsed/refractory indolent non-Hodgkin lymphoma.2
“Because advanced age at diagnosis is a risk factor in patients with indolent non-Hodgkin lymphoma, we performed posthoc subgroup analyses by age from AUGMENT, and data here focused on patients aged more than 70 years,” Trněny explained as the rationale for the subgroup analyses.
The double-blind, phase III AUGMENT trial included 358 patients with relapsed/refractory follicular lymphoma or MZL in need of treatment. Across the study, 295 patients had follicular lymphoma and 63 patients had MZL. Patient had to have received ≥1 prior chemotherapy, immunotherapy, or chemoimmunotherapy regimen, and could not be rituximab refractory.
Patients were randomized to rituximab at 375 mg/m2
on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2 through 5, plus either 20 mg of lenalidomide/daily on days 1 through 21 every 28 days for up to 12 cycles (n = 178) or placebo (n = 180).
In the intent-to-treat population, patient characteristics at baseline were well balanced overall between the 2 arms. The median age was 63 years; over 70% of patients had advanced-stage disease at study entry. About 50% of patients had high tumor burden per the GELF criteria. Around 83% of patients in each arm had follicular lymphoma, with the remaining 17% having MZL; 34.5% of patients had a FLIPI score ≥3.
The posthoc analysis stratified patients who were ≥70 years (n = 91) and received R2
(n = 47) or placebo (n = 44). Here, the median age was 75 years, and 55% of patients on R2
had an ECOG performance status of 1 to 2 versus 36% of patients who received rituximab plus placebo. Additionally, about half of patients in each arm had a FLIPI score ≥3, and about three-fourths of patients had follicular lymphoma.
In the ITT population, 57% of patients on R2
received 1 prior systemic regimen, 17% had received 2, and 25% had received ≥3. In the control arm, the corresponding rates were 54%, 23%, and 23%, respectively. Eighty-five percent of patients in the R2
arm and 83% of patients in the placebo arm had prior rituximab. About 75% of patients in each arm had received a prior rituximab-containing chemotherapy regimen. Thirty-seven percent of patients in the R2
arm and 42% of patients in the placebo arm had progressed within 2 years of their last regimen.
In the ≥70-year subgroup, 53% of patients on R2
received >1 prior systemic therapy compared with 39% for those who received rituximab 39%; furthermore, 36% and 14% of patients, respectively, relapsed ≤2 years following their initial diagnosis. Trněny explained these were notable differences between the 2 arms. However, 85.5% of patients received prior rituximab, and 66% received a prior rituximab-containing regimen. Fifteen percent of patients on R2
were refractory to their last regimen versus 7% who were randomized to receive rituximab with placebo.