Results of a phase I trial indicate that obinutuzumab can be safely combined with venetoclax in patients with previously untreated follicular lymphoma (FL); however, the researchers did not recommend further development of the drug combination in this patient population.
“While the two drugs could be safely combined and no new safety signals were identified, our results do not provide any clear benefit by adding venetoclax to anti-CD20 monoclonal antibody in patients with previously untreated FL,” researchers wrote.
The study evaluated two dose levels of venetoclax in 25 patients with previously untreated grade 1-3a FL. Dose level 1 was venetoclax 600 mg once daily and dose level 2 was venetoclax 800 mg once daily, starting on day 2 of cycle 1 continuously for six 28-day cycles.
Only one patient treated at the dose level 2 had a dose-limiting toxicity: grade 4 thrombocytopenia after first obinutuzumab infusion.
Based on this, the recommended phase II dose of the combination is venetoclax 800 mg once daily continuously for six cycles starting on day 2 of cycle 1 with obinutuzumab 1,000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2-6 followed by obinutuzumab maintenance for up to two years.
Eighteen serious adverse events occurred in 11 patients; nine were considered at least possibly related to study treatment. These events were grade 3 febrile neutropenia (n=2), grade 1 fever (n=1), grade 3 bronchial infection (n=1), grade 3 upper respiratory infection (n=1), grade 3 aspartate aminotransferase (n=1), grade 4 thrombocytopenia (n=1), grade 3 pneumonitis (n=1), and COVID-19 infection (n=1).
Response was evaluated by CT in 24 patients at six months. By CT evaluation, the overall response rate (ORR) was 87.5%, with a complete response rate of 25%. Response was evaluated with PET/CT in 19 patients; the ORR was 84.2%, with a complete response rate of 68.4%.
At 30 months, complete response by CT was still 25.0%. According to PET/CT, complete response was 52.6%. One-year progression-free survival (PFS) was 77.8% for CT evaluable patients and 79% and PET/CT evaluable patients. At 30 months, the PFS rates were 73.2% and 79.0%, respectively.
“The observed one-year and 30-months PFS were lower if compared to other anti-CD20-based combinations, thus we were not able to provide any evidence of benefit by adding venetoclax to obinutuzumab in this setting,” the researchers concluded.
Stathis A, Mey UJM, Schar S, et al. SAKK 35/15: a phase 1 trial of obinutuzumab in combination with venetoclax in patients with previously untreated follicular lymphoma. Blood Adv. 2022. doi:10.1182/bloodadvances.2021006520.
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