Atezolizumab combined with immunogenic salvage chemoimmunotherapy in patients with transformed diffuse large B-cell lymphoma

Haematologica. 2025 Jan 1;110(1):142-152. doi: 10.3324/haematol.2024.285185.

Abstract

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) transformed from indolent B-cell lymphomas, including Richter transformation, have a poor prognosis. PD-1/PD-L1 antibodies produce modest objective and complete response rates in B-cell non-Hodgkin lymphoma as monotherapy but may synergize with immunogenic chemotherapies such as gemcitabine and oxaliplatin (GemOx). Thus, we evaluated the safety and efficacy of atezolizumab plus rituximab and GemOx (R-GemOx+Atezo) in R/R transformed DLBCL, including Richter transformation. We conducted a phase I trial including patients with transformed DLBCL after ≥1 prior therapy. Patients received up to four cycles of R-GemOx+Atezo. Patients in complete remission could then proceed to R-Atezo maintenance until progression. A safety lead-in with evaluation of dose-limiting toxicity was performed to confirm the recommended phase II dose; subsequently the treatment was administered to two expansion cohorts: one with transformed follicular lymphoma (FL) and the other with non-FL transformed DLBCL, including Richter transformation. Twenty-seven patients were enrolled. One of the six patients in the safety lead-in had a dose-limiting toxicity attributed to atezolizumab, a grade 4 Stevens-Johnson syndrome. The most common grade ≥3 events were neutropenia (18.5%), lymphopenia (18.5%), and thrombocytopenia (14.8%). The overall and complete response rates were 59% and 33%, respectively. The overall and complete response rates in transformed FL were 79% and 43%, respectively, and 38% and 23% in transformed non-FL, respectively. The median progression-free survival and overall survival of the total population were 4.2 and 7.7 months, respectively. R-GemOx+Atezo was well tolerated and demonstrated promising preliminary efficacy in patients with relapsed/refractory transformed DLBCL.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Gemcitabine
  • Humans
  • Immunotherapy / methods
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / therapy
  • Male
  • Middle Aged
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / therapeutic use
  • Rituximab / administration & dosage
  • Rituximab / therapeutic use
  • Salvage Therapy*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • atezolizumab
  • Gemcitabine
  • Deoxycytidine
  • Oxaliplatin
  • Rituximab