Combination of atezolizumab and tazemetostat in patients with relapsed/refractory diffuse large B-cell lymphoma: Results from a phase Ib study Journal Article


Authors: Palomba, M. L.; Cartron, G.; Popplewell, L.; Ribrag, V.; Westin, J.; Huw, L. Y.; Agarwal, S.; Shivhare, M.; Hong, W. J.; Raval, A.; Chang, A. C.; Penuel, E.; Morschhauser, F.
Article Title: Combination of atezolizumab and tazemetostat in patients with relapsed/refractory diffuse large B-cell lymphoma: Results from a phase Ib study
Abstract: Background: The combination of atezolizumab, a monoclonal antibody that targets programmed death-ligand 1 (PD-L1) and inhibits the interaction between PD-L1 and its receptors, and tazemetostat, an EZH2 inhibitor, may lead to selective epigenetic reprogramming, alter the tumor microenvironment, and provide additive or synergistic response to patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Materials and Methods: This was an open-label, phase Ib study assessing the safety, tolerability, and preliminary efficacy of atezolizumab plustazemetostat in patients with R/R DLBCL. Atezolizumab (1200 mg) was administered via intravenous (IV) infusion on day 1 of each cycle and tazemetostat (800 mg) was given orally twice daily (BID) on days 1 to 21. Primary endpoints were safety and tolerability, and to identify a recommended phase II dose (RP2D) for atezolizumab. Secondary efficacy endpoints included response rate and duration of response. Results: A total of 43 patients were enrolled, receiving a median of 3 prior lines of treatment (range: 1-9). The RP2D for atezolizumab was 1200 mg IV infusion every 3 weeks in combination with tazemetostat 800 mg BID. At the RP2D, adverse events reported in ≥20% patients were anemia(11 patients [26%]), fatigue (10 patients [23%]), and nausea (10 patients [23%]). Overall response rate was 16% (complete response rate: 7%). Median progression-free survival was 2 months (range: 0-24) and median overall survival was 13 months (range: 1-29). Conclusions: The combination of atezolizumab and tazemetostat was determined to be safe and tolerable. However, anti-tumor activity of the combination was modest. © 2022 The Authors
Keywords: immunotherapy; non-hodgkin's lymphoma; diffuse large b-cell lymphoma; epigenetic; ezh2 inhibitor
Journal Title: Clinical Lymphoma, Myeloma and Leukemia
Volume: 22
Issue: 7
ISSN: 2152-2650
Publisher: Elsevier Inc.  
Date Published: 2022-07-01
Start Page: 504
End Page: 512
Language: English
DOI: 10.1016/j.clml.2021.12.014
PUBMED: 35151584
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 July 2022 -- Source: Scopus
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  1. Maria Lia Palomba
    416 Palomba