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. 2022 Feb;115(2):222-232. doi: 10.1007/s12185-021-03241-4. Epub 2021 Nov 19.

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.

Keywords: Diffuse large B-cell lymphoma; Durvalumab; High risk; R-CHOP.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Middle Aged
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Treatment Outcome
  • Vincristine / adverse effects
  • Vincristine / therapeutic use

Substances

  • Antibodies, Monoclonal
  • R-CHOP protocol
  • durvalumab
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone