Adding atezolizumab to treatment with obinutuzumab and bendamustine does not improve progression-free survival (PFS) in patients with previously untreated follicular lymphoma (FL), according to research published in Blood Advances.
The PFS observed with atezolizumab plus obinutuzumab and bendamustine was no better than the PFS previously reported with obinutuzumab and bendamustine in the GALLIUM trial. In addition, atezolizumab plus obinutuzumab and bendamustine was associated with an increased risk of adverse events (AEs).
Researchers conducted a phase 1b/2 trial to evaluate the safety and efficacy of atezolizumab plus obinutuzumab and bendamustine in adults with previously untreated FL (ClinicalTrials.gov Identifier: NCT02596971).
The primary endpoint was complete response (CR) rate on PET-CT at the end of induction (by independent review committee [IRC] using modified Lugano 2014 criteria). Secondary endpoints included investigator-assessed PFS and overall survival (OS).
The investigators included a safety run-in phase followed by an expansion phase with atezolizumab plus obinutuzumab and bendamustine. The induction treatment comprised intravenous infusions of atezolizumab (840 mg on days 1 and 15 of cycles 2 to 6), obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1 and day 1 of cycles 2 to 6), and bendamustine (90 mg/m2 on days 1 and 2 of cycles 1 to 6) in 28-day cycles.
Patients who achieved a CR or partial response (PR) at the end of induction were given maintenance therapy (atezolizumab at 840 mg on days 1 and 2 of each month and obinutuzumab at 1000 mg on day 1 of every other month) for up to 24 months or until disease progression or unacceptable toxicity.
A total of 40 patients with previously untreated FL were enrolled and treated. The median age was 56.5 years (range, 29-75), 50% of patients were women, 85.0% were White, and 92.5% had advanced-stage disease.
The IRC-assessed CR rate was 75.0%. According to investigator assessment, the 3-year OS rate was 89.3%, and the 3-year PFS rate was 80.9%. In comparison, the 3-year PFS rate was 84.0% with obinutuzumab and bendamustine in the phase 3 GALLIUM trial.
In the present study, grade 3-5 AEs were reported in 32 patients (80%), with grade 5 AEs occurring in 5 patients (12.5%). AEs of special interest related to atezolizumab included pneumonitis, colitis, endocrinopathies, hepatitis, systemic lupus erythematosus, neurological disorders, hypersensitivity reactions, nephritis, ocular toxicities, myositis, myopathies, vasculitis, grade 2 or higher cardiac disorders, and severe cutaneous reactions.
“Although effective in the first-line treatment of FL, the combination of [atezolizumab-obinutuzumab-bendamustine] does not appear to offer a significant clinical benefit over that achievable with [obinutuzumab-bendamustine] alone,” the researchers wrote. “Furthermore, the addition of [atezolizumab] to [obinutuzumab-bendamustine] appears to carry an increased risk of clinically significant AEs, particularly immune-related AEs. Therefore, due to the unfavorable safety profile, [atezolizumab-obinutuzumab-bendamustine] should not be recommended in patients with previously untreated FL.”
Disclosures: This research was supported by F. Hoffmann-La Roche Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Younes A, Burke JM, Diefenbach C, et al. Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma. Blood Adv. 2022;6(20):5659-5667. doi:10.1182/bloodadvances.2021006131
This article originally appeared on Hematology Advisor