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

Grzegorz S. Nowakowski, Wolfgang Willenbacher, Richard Greil, Thomas S. Larsen, Krish Patel, Ulrich Jäger, Robert F. Manges, Lorenz Trümper, Hele Everaus, Nagesh Kalakonda, Peter Brown, Judit Meszaros Jørgensen, David Cunningham, Justine Dell’Aringa, Brian Fox, Neus Domper Rubio, Nurgul Kilavuz, Marie Laure Casadebaig, Oliver Manzke, Javier Munoz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Pages (from-to)222-232
Number of pages11
JournalInternational Journal of Hematology
Volume115
Issue number2
DOIs
StatePublished - Feb 2022

Keywords

  • Diffuse large B-cell lymphoma
  • Durvalumab
  • High risk
  • R-CHOP

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