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

• Published in: International journal of hematology 2022-02, Vol.115 (2), p.222-232
• Main Authors: Nowakowski, Grzegorz S., Willenbacher, Wolfgang, Greil, Richard, Larsen, Thomas S., Patel, Krish, Jäger, Ulrich, Manges, Robert F., Trümper, Lorenz, Everaus, Hele, Kalakonda, Nagesh, Brown, Peter, Jørgensen, Judit Meszaros, Cunningham, David, Dell’Aringa, Justine, Fox, Brian, Rubio, Neus Domper, Kilavuz, Nurgul, Casadebaig, Marie-Laure, Manzke, Oliver, Munoz, Javier
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antitumor activity; Apoptosis; B-cell lymphoma; Biomarkers; Cancer therapies; Chemotherapy; Consolidation; Cyclophosphamide; Cytotoxicity; Doxorubicin; Gene expression; Health risks; Hematology; Hospitals; Immune checkpoint; Immunotherapy; Ligands; Lymphocytes B; Lymphoma; Medical research; Medicine; Medicine & Public Health; Monoclonal antibodies; Oncology; Original Article; Prednisone; Risk; Rituximab; Safety; Targeted cancer therapy; Vincristine
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-021-03241-4

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 (R 2 -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 R 2 -CHOP (ABC), then durvalumab consolidation (1500 mg every 28 days). Of 46 patients, 43 received R-CHOP and three R 2 -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.