Atezolizumab, Venetoclax, and Obinutuzumab Show Promise in Richter Transformation DLBCL
Key Insights
A phase II trial (MOLTO) demonstrated that atezolizumab, venetoclax, and obinutuzumab achieved a 67.9% objective response rate in patients with Richter transformation diffuse large B-cell lymphoma (search) (DLBCL-RT (search)).
After 12 months, progression-free survival was 42.9% overall, with 87.5% in patients achieving complete remission, highlighting the regimen's potential for durable responses.
The combination therapy showed a manageable safety profile, with neutropenia being the most common adverse event, and no treatment-related deaths were reported.
Atezolizumab, venetoclax, and obinutuzumab have demonstrated promising activity in patients with Richter transformation diffuse large B-cell lymphoma (search) (DLBCL-RT (search)), according to results from the phase II MOLTO trial. The study, published in The Lancet Oncology, found that the combination therapy achieved a clinically significant overall response rate, suggesting a potential new first-line treatment approach for this aggressive lymphoma subtype.
The trial enrolled 28 patients across sites in Italy and Switzerland between October 2019 and October 2022. Participants received obinutuzumab, atezolizumab, and continuous venetoclax over 21-day cycles. The primary outcome was overall response rate at day 21 of cycle 6, with a target of at least 67% to indicate clinical activity.
Efficacy Outcomes
After a median follow-up of 16.8 months, the objective response rate at cycle 6 was 67.9% (95% CI = 47.6%-84.1%), with a complete response rate of 28.6%. Among responders at cycle 6, 57.9% maintained their response at 12 months. The best complete response rate observed was 35.7%, with some patients converting from partial to complete remission after cycle 6.
At 12 months, progression-free survival was 42.9% (95% CI = 24.6%-60.0%), and overall survival was 64.3% (95% CI = 43.8%-78.9%). Notably, progression-free survival at 12 months was 87.5% among patients who achieved complete remission, compared to 36.4% in those with partial remission.
Safety Profile
The most common adverse events of any grade were neutropenia (43%), neutropenic fever (18%), and COVID-19 infection (18%). Grade ≥ 3 adverse events occurred in 61% of patients, most commonly neutropenia (39%) and thrombocytopenia (11%). Serious adverse events occurred in 29% of patients, with infections being the most frequent (18%). Importantly, no treatment-related deaths were observed, and immune-related adverse events occurred in 21% of patients without leading to treatment discontinuation. Tumor-lysis syndrome was not observed.
Investigator Commentary
The investigators concluded that the combination of atezolizumab, venetoclax, and obinutuzumab was active and safe, suggesting its potential as a new first-line, chemotherapy-free treatment option for patients with DLBCL-RT (search). Alessandra Tedeschi, MD, of ASST Grande Ospedale Metropolitano Niguarda, Niguarda Cancer Center, Milan, is the corresponding author of the publication.