Bendamustine plus obinutuzumab induction therapy has shown improved complete response (CR) rates compared to bendamustine plus rituximab (BR) in patients with previously untreated mantle cell lymphoma (MCL). The phase 2 trial results, published in Clinical Lymphoma, Myeloma & Leukemia, suggest a potential shift in treatment approach for MCL patients ineligible for intensive therapy.
Progression-Free Survival and MRD Assessment
At a median follow-up of 43.9 months (95% CI, 28.3-60.1), the median progression-free survival (PFS) was 46.5 months (95% CI, 35.1–NA). The 2- and 3-year PFS rates were 66.0% (95% CI, 41.6%-82.2%) and 58.7% (95% CI, 33.2%-77.3%), respectively. Notably, the omission of maintenance obinutuzumab in patients who achieved minimal residual disease (MRD) negativity did not lead to worse outcomes compared to those who received maintenance obinutuzumab (HR, 0.45; 95% CI, 0.10-1.91; P = .28).
According to lead study author Julie E. Chang, MD, associate professor at the University of Wisconsin (UW) School of Medicine and Public Health, “These data support the notion that MRD assessment is a reasonable approach to identify patients with more favorable disease for whom maintenance may not be needed in order to preserve PFS and allow for minimization of treatment-related toxicity in an often older and less-fit population.”
Trial Design and Patient Characteristics
The phase 2 trial enrolled 21 patients with MCL ineligible for intensive therapy between February 2018 and January 2022. The study included patients at least 60 years of age, or younger patients with comorbidities limiting tolerance to intensive therapies. All patients received intravenous bendamustine at 90 mg/m2 on days 1 and 2 of each 28-day cycle for 4 to 6 cycles, along with obinutuzumab during cycle 1. Following induction therapy, patients achieving an objective response received consolidation intravenous obinutuzumab. MRD assessment determined the need for maintenance therapy.
Key patient characteristics included a median age of 70 years, with 76% being men and 95% having stage IV disease. The median MCL International Prognostic Index (MIPI) score was 6.11, with 66.7% of patients having high-risk disease by MIPI. Additionally, 38.1% of patients had a Ki-67 proliferative index above 30%.
Efficacy and Safety Outcomes
The overall response rate was 95%, including a 75% CR rate and a 20% partial response (PR) rate. The 2- and 3-year OS rates were 75.4% (95% CI, 50.6%-89.0%) and 60.9% (95% CI, 33.9%-79.7%), respectively. The toxicity profiles were consistent with previous trials utilizing obinutuzumab-based regimens. Common adverse effects included leukopenia, nausea, neutropenia, and anemia.
Implications for MCL Treatment
The study suggests that bendamustine combined with obinutuzumab is a viable alternative to bendamustine plus rituximab in previously untreated MCL, offering higher CR rates and significant MRD negativity. Early MRD evaluation may also serve as a prognostic marker, potentially guiding tailored treatment strategies.
“Our results demonstrate that the combination of bendamustine with obinutuzumab is a reasonable alternative treatment option to BR in previously untreated MCL, with higher rates of CR and 50% rates of MRD negativity in the marrow and blood. Additionally, we found that MRD evaluation during early induction therapy may be a prognostic marker identifying patients with a more indolent disease course, and warrants further investigation,” the authors concluded.
