Combination atezolizumab, obinutuzumab, and venetoclax appears to produce durable responses in a subset of previously untreated patients with the diffuse large B-cell lymphoma variant of Richter syndrome (DLBCL-RS), according to research presented at the ASCO Annual Meeting 2023.

For the open-label phase 2 MOLTO study ( Identifier: NCT04082897), researchers are evaluating the safety and efficacy of combination atezolizumab, obinutuzumab, and venetoclax in the previously untreated DLBCL-RS setting.

Researchers presented primary endpoint findings for the overall response rate (ORR) from MOLTO. Overall, 28 patients were enrolled between 2019 and 2022. In this cohort, the median age was 70 years (range, 32-81), 71.4% of patients had received prior treatment for chronic lymphocytic leukemia, and 42.9% of patients had 17p deletion or a TP53 mutation.

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The median follow-up was 11.6 months. At this point, the ORR was 67.9%, meeting the study’s primary endpoint; the complete response rate was 28.6%. Three patients were not evaluable for ORR because of early withdrawal (2 patients) and grade 5 infection (1 patient).

At time of analysis, 11 of 19 responders (57.9%) were in continuous remission and 8 were on active therapy. The median duration of response was 11.7 months; median progression-free survival and overall survival were 16.2 and 31.6 months, respectively.

Further analysis showed that bulky disease and an Eastern Cooperative Oncology Group performance status greater than 1 affected progression-free survival (P =.0475 and P =.0195, respectively).

There were 43 grade 3 or 4 adverse events noted in 60.7% of patients, of which 51.2% were hematological. Grade 3 or worse infections were also noted in 6 patients, 2 of which were grade 5. One patient developed myelodysplastic syndrome.

“Venetoclax, atezolizumab, and obinutuzumab should be effective in [previously untreated] patients with Richter transformation and allowed us to achieve the primary endpoint of this study of an ORR greater than 67%,” said Anna Maria Frustaci, MD, of the Department of Hematology at the Niguarda Cancer Center in Milan, Italy, when presenting the study’s findings.

MOLTO is actively recruiting patients as of June 6, 2023.

Disclosures: This research was supported by Roche. Please see the original reference for a full list of disclosures.


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. ASCO 2023. June 2-6, 2023. Abstract 7502.