According to findings from the phase 2 MOLTO trial, atezolizumab, obinutuzumab, and venetoclax combination treatment yielded durable remissions lasting longer than 2 years among patients with untreated diffuse large B-cell lymphoma (DLBCL) variant of Richter syndrome (RS). 

At the 2023 American Society of Clinical Oncology conference in Chicago, Illinois, Anna Maria Frustaci, MD, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy, and coauthors presented the data from this study. 

Dr Frustaci and coauthors stated, “Chemoimmunotherapy is the standard first line of patients (pts) with diffuse large B-cell lymphoma variant of Richter syndrome.” However, “response rate and duration are unsatisfactory.” The study authors aimed to investigate non-chemotherapy combination treatments that may be able to treat DLBCL variant of RS, such as atezolizumab, a humanized monoclonal antibody blocking PD-L1, venetoclax, a BCL2 inhibitor, and obinutuzumab, an anti-CD20 MoAb. 

The primary endpoint was an overall response rate of at least 67% at cycle 6. Secondary endpoints included complete response rate, duration of response, progression-free survival, overall survival, the impact of mutations, and the relationship between chronic lymphocytic leukemia-RS clonality and outcomes. 

28 patients with diffuse large B-cell lymphoma (DLBCL) variant of Richter syndrome were enrolled in this trial and received 35 cycles of obinutuzumab at 1000 mg during cycles 1 through 8, atezolizumab at 1200 mg during cycles 1 through 8, and venetoclax at 400 mg/d during cycles 1 through 35. 

At the data cutoff, the overall response rate was 67.9% (n = 19), which met the primary endpoint. The complete response rate was 28.6%. At a median follow-up of 11.6 months, 57.9% of patients who reached an overall response (n = 11/19) achieved continuous remission, with 8 patients remaining on active therapy, 2 undergoing allogeneic transplant, and 1 discontinuing treatment due to myelodysplastic syndrome. The median duration of response was 11.7 months, and the median progression-free survival was 16.2 months. Among the 13 patients who progressed, 4 received salvage therapy. Grade 3 to 4 adverse events were observed in 60.7% of patients (n = 17), the most common being hematological events (51.2%). Infections ≥ grade 3 occurred in 6 patients. 

As endpoints were met, Dr Frustaci et al concluded, “Atezolizumab, obinutuzumab and venetoclax combination is active in [patients] with untreated DLBCL-RS. This regimen led to durable remissions, longer than 2 [years] in one third of responders.” 

Source: 

Frustaci AM, Montillo M, Rossi D, et al. Results of MOLTO, a multicenter, open label, phase II clinical trial evaluating venetoclax, atezolizumab and obinutuzumab combination in Richter syndrome. Presented at the ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract 219929