Results of MOLTO, a multicenter, open label, phase II clinical trial evaluating venetoclax, atezolizumab and obinutuzumab combination in Richter syndrome.

作者：A. Frustaci, M. Montillo, D. Rossi, P. Zinzani, M. Motta, G. Gaidano, G. Quaresmini, L. Scarfò, D. Pietrasanta, M. Coscia, M. Deodato, G. Zamprogna, R. Cairoli, G. Stüssi, E. Zucca, S. Pileri, T. Zenz, A. Tedeschi · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.7502 · 被引用次数：10

7502 Background: Chemoimmunotherapy is the standard first line of patients (pts) with diffuse large B-cell lymphoma (DLBCL) variant of Richter syndrome (RS). Response rate and duration are unsatisfactory. The biology of RS (high rate of DNA damage response pathway defects, high tumor mutation burden coupled with the expression of the PD1/PDL1 axis) prompts investigation of non-chemo combinations leveraging agents that circumvent TP53 abnormalities and trigger anti tumor immune response. MOLTO is a multicenter international ph 2 study (NCT04082897) evaluating activity and safety of atezolizumab (humanized monoclonal antibody blocking PD-L1), venetoclax (BCL2 inhibitor) and obinutuzumab (anti-CD20 MoAb) combination in untreated DLBCL-RS. Methods: Treatment consisted of 35 cycles with obinutuzumab (1000 mg C1-8), atezolizumab (1200 mg C1-18) and venetoclax (400 mg/d C1-35), q21. Primary endpoint was ORR ≥67% at C6. RS diagnosis was centrally revised. RS mutation profile was tested on pre-treatment cell free DNA. Minimal residual disease (MRD) was tested by 12 colors flow cytometry and NGS on peripheral blood mononuclear cells and plasma. Results: 28 planned pts were enrolled from Oct 2019 to Oct 2022 (Table). Three were not evaluable for primary endpoint due to G5 infection (n=1) or early withdrawn (n=2). As per intention-to-treat ORR was 67.9% (19/28) thus meeting primary endpoint. CR rate was 28.6%. No clinical characteristics influenced C6-ORR. After a median follow-up of 11....