A phase-II study of atezolizumab in combination with obinutuzumab or rituximab for relapsed or refractory mantle cell or marginal zone lymphoma or Waldenström’s macroglobulinemia

Abstract

We report efficacy, safety and biomarker data from a phase-II study evaluating atezolizumab (eight 21-day cycle as induction therapy) in combination with obinutuzumab in patients with relapsed/refractory mantle cell lymphoma (MCL, n = 30) or Waldenström’s macroglobulinemia (WM, n = 4), and in combination with rituximab in patients with marginal zone lymphoma (MZL, n = 21). All patients received atezolizumab monotherapy as maintenance for ≤10 cycles. Objective response rates at end of induction were 16.7% (MCL) and 42.9% (MZL), with no responses in WM. Median duration of response was 6.8 months (range 5.7–not estimable) for MCL and not reached for MZL. Treatment-emergent adverse events (TEAEs) occurred in 93.3%, 95.2% and 100% of MCL, MZL and WM patients, respectively. One fatal TEAE (pneumonia) occurred in each of the MCL and MZL groups. Biomarker analysis highlighted the importance of characterizing the immune environment to optimize efficacy of immunotherapy regimens.

Trial registration details: EudraCT: 2016-003579-22

Keywords:

• Atezolizumab
• obinutuzumab
• rituximab
• lymphoma
• Waldenström’s macroglobulinemia

Acknowledgements

TEGAR was sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of Christian Buske, was provided by Helen Cathro, PhD, of Ashfield MedComms, an Ashfield Health company and was funded by F. Hoffmann-La Roche Ltd. The authors would like to thank Professor Andrey Zaritskey for his contributions to this study.

Disclosure statement

PP has received honoraria from AbbVie, Genesis, Gilead, Janssen, Novartis and Roche, and research support from AbbVie, Astellas, Genesis and Roche. CT has received honoraria from AbbVie, Gilead Sciences, Incyte, Janssen, Novartis and Roche. VVP has received honoraria from AbbVie, Generium, Janssen, Roche, Sanofi and Takeda, has received travel expenses from Janssen and Sanofi, has participated in advisory boards for Janssen and Takeda, and has taken a leadership or fiduciary role for the Russian Oncohematology Society. AM-N has received honoraria from AbbVie, Amgen, Celgene, Gilead/Kite, Janssen, Kiowa Kirin, Roche, Takeda and Werfen, has received payment for expert testimony from Janssen, Kiowa Kirin and Janssen, has received travel expenses from Janssen, Kiowa Kirin, Roche, Takeda and Werfen, and has participated in advisory boards for Gilead/Kite, Janssen, Kiowa Kirin, Roche and Takeda. RG-S has received honoraria from Astellas, Beigene, Gilead, Incyte, Janssen, Novartis and Takeda, acted as a consultant for Astellas, Janssen and Takeda, has received research funding from AstraZeneca, Gilead and Takeda, holds patents, royalties or other intellectual property from IVS Technologies wrt BIOMED 2 Priers, has received payment for expert testimony from IVS Technologies, and has received travel expenses from Janssen and Takeda. SLG has received honoraria from and acted as a consultant for Roche. AS has received institutional research funding for clinical trials from AbbVie, ADC Therapeutics, Bayer, Cellestia, MEI Therapeutics, Merck, Novartis, Pfizer, Philogen and Roche, has acted as a consultant for Bayer, Debiopharm and Eli Lilly, and has participated in advisory boards for Roche. CB has received research funding from Amgen, Bayer, Celltrion, Janssen, MSD, and Roche, and honoraria from Amgen, Beigene, Celltrion, Janssen, Morphosys, MSD, Pfizer, Regeneron and Roche. PK, TP, and JCW are employees of F. Hoffmann-La Roche Ltd. AB is an employee of and holds stock in F. Hoffmann-La Roche Ltd. HH in an employee of Genentech, Inc. and holds equity in Genentech, Inc. GT has no relationships to disclose.

Data availability statement

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Additional information

Funding

This work was supported and funded by F. Hoffmann-La Roche Ltd.