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Safety and efficacy of durvalumab with R-CHOP or R2-CHOP in untreated, high-risk DLBCL: a phase 2, open-label trial

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Abstract

Patients with high-risk diffuse large B-cell lymphoma (DLBCL) have poor outcomes following first-line cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP). Evidence shows chemotherapy and immune checkpoint blockade can increase antitumor efficacy. This study investigated durvalumab, a programmed death-ligand 1 inhibitor, combined with R-CHOP or lenalidomide + R-CHOP (R2-CHOP) in newly diagnosed high-risk DLBCL. Patients received durvalumab 1125 mg every 21 days for 2–8 cycles + R-CHOP (non-activated B-cell [ABC] subtype) or R2-CHOP (ABC), then durvalumab consolidation (1500 mg every 28 days). Of 46 patients, 43 received R-CHOP and three R2-CHOP. All patients had the high-risk disease; 14 (30.4%) and eight (17.4%) had double- or triple-hit DLBCL, respectively. Following induction, 20/37 (54.1%) patients receiving durvalumab + R-CHOP achieved complete response (CR), and seven (18.9%) partial response (PR); 25 (67.6% [95% CI 50.2–82.0]) continued to consolidation and were progression-free at 12 months. Among efficacy-evaluable patients with double- or triple-hit DLBCL (n = 12), five achieved CR and five PR. Adverse events were generally consistent with R-CHOP. Correlative analyses did not identify conclusive biomarkers of response. Durvalumab + R-CHOP is feasible in DLBCL with no new safety signals, but the combination provided no greater benefit than R-CHOP.

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Acknowledgements

The authors thank the patients enrolled in the study as well as associated clinical trial teams. The authors received editorial support in the preparation of this manuscript from Lauren Gallagher, RPh, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, sponsored by Celgene, a Bristol Myers Squibb Company, Princeton, NJ, USA. The authors, however, directed and are fully responsible for all content and editorial decisions for this manuscript.

Funding

This trial (NCT03003520) was sponsored by Celgene, a Bristol Myers Squibb company, and supported by AstraZeneca/MedImmune.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic Rochester, 200 1st St SW, Rochester, MN, 55902, USA

    Grzegorz S. Nowakowski

  2. Internal Medicine, Hematology and Oncology Department, Innsbruck Medical University, Innsbruck, Austria

    Wolfgang Willenbacher

  3. Oncotyrol, Center for Personalized Cancer Medicine, Innsbruck, Austria

    Wolfgang Willenbacher

  4. Salzburg Cancer Research Institute and Cancer Cluster, Paracelsus Medical University Salzburg, Salzburg, Austria

    Richard Greil

  5. Department of Hematology, Odense University Hospital, Odense, Denmark

    Thomas S. Larsen

  6. Swedish Cancer Institute Hematology and Oncology Department, Center for Blood Disorders and Stem Cell Transplantation, Seattle, WA, USA

    Krish Patel

  7. Division of Hematology and Hemostseology, Medical University of Vienna, Vienna, Austria

    Ulrich Jäger

  8. Parkview Health, Parkview Cancer Institute, Hematology Tumor Site, Fort Wayne, IN, USA

    Robert F. Manges

  9. Department of Hematology‐Oncology, Universitätsmedizin Göttingen, Göttingen, Germany

    Lorenz Trümper

  10. Haematology and Oncology Clinic, Tartu University Hospital, Tartu, Estonia

    Hele Everaus

  11. University of Liverpool and The Clatterbridge Cancer Centre, Liverpool, UK

    Nagesh Kalakonda

  12. Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Peter Brown

  13. Aarhus University Hospital, Aarhus, Denmark

    Judit Meszaros Jørgensen

  14. The Royal Marsden Hospital, The Institute of Cancer Research, Sutton, Surrey, UK

    David Cunningham

  15. Celgene International, Boudry, Switzerland

    Justine Dell’Aringa, Brian Fox, Neus Domper Rubio, Nurgul Kilavuz, Marie-Laure Casadebaig & Oliver Manzke

  16. Banner MD Anderson Cancer Center, Phoenix, AZ, USA

    Javier Munoz

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  1. Grzegorz S. Nowakowski
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Correspondence to Grzegorz S. Nowakowski.

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Conflict of interest

GSN has received grants from Celgene/Bristol Myers Squibb, Curis, Incyte, MorphoSys, Roche, and Seattle Genetics, and personal fees from Debiopharm, Karyopahrm, Kite, Kymera, Selvita, and TG Therapeutics. WW has served on steering and safety committees for Amgen, Celgene, DSMM, and Morphosys; was employed by Oncotyrol (20%); has served on advisory boards and as a consultant for Amgen, Bristol Myers Squibb/Celgene, Gilead, GSK, Incyte, Janssen, Novartis, Merck, Pfizer, Roche, Sandoz, Sanofi, and Takeda; has presented lectures for Amgen, AbbVie, Bristol Myers Squibb/Celgene, Fujimoto, Gilead, GSK, Janssen, Myelom- und Lymphomselbsthilfe Österreich, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Takeda; and has received research funding from Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, Roche, Sanofi, Takeda, oncotyrol, European Commission (FP7—OPTATIO), and Bundesland Tirol Programm “Translational research.” RG has received honoraria, consulting/advisory fees, research funding, and travel fees, accommodations, and/or expenses from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Gilead, Merck, MSD, Novartis, Roche, Sandoz, and Takeda. TSL has served as a consultant and on advisory boards for Bristol Myers Squibb/Celgene, Novartis, Roche, and Gilead. KP has received grants and/or personal fees from AstraZeneca, Bristol Myers Squibb, Genentech, Kite Pharmaceuticals, Pharmacyclics/Janssen, and TG Therapeutics. UJ has served on the advisory board for Bristol Myers Squibb/Celgene, Roche, Novartis, and Janssen; and has served as a consultant for Miltenyi, Takeda, Merck, Incyte, and AbbVie. RFM, LT, and HE have nothing to disclose. NK has received research funding from Celgene and Roche UK, and has served on the advisory board for Bristol Myers Squibb, Gilead, Karyopharm, and Takeda. PB has served on the advisory board for Celgene, Incyte, Takeda, and Roche. JMJ has received personal fees from Bristol Myers Squibb/Celgene, Gilead/Kite Pharma, Novartis, and Roche. DC has received research funding from Amgen, AstraZeneca, Bayer, Celgene, Clovis, Eli Lilly, Janssen, MedImmune, Merck, Merrimack, Sanofi, and 4SC. BF, NDR, NK, and M-LC are employees of and stockholders in Bristol Myers Squibb. JD, NK, and OM were employees of and stockholders in Bristol Myers Squibb at the time of the study. JM has served as a consultant for Pharmacyclics, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa, Alexion, Beigene, Fosunkite, Innovent, Seattle Genetics, and Beigene; has received research funding from Bayer, Gilead/Kite Pharma, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, and Millennium; has received honoraria from Kyowa and Seattle Genetics; and has served on the speakers bureau for Gilead/Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/Bristol Myers Squibb, Genentech/Roche, and AbbVie.

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Justine Dell’Aringa, Nurgul Kilavuz and Oliver Manzke: At the time of the study.

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Nowakowski, G.S., Willenbacher, W., Greil, R. et al. Safety and efficacy of durvalumab with R-CHOP or R2-CHOP in untreated, high-risk DLBCL: a phase 2, open-label trial. Int J Hematol 115, 222–232 (2022). https://doi.org/10.1007/s12185-021-03241-4

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