Page 150 - Haematologica Vol. 110 - January 2025

ARTICLE - Non-Hodgkin Lymphoma
Atezolizumab combined with immunogenic salvage chemoimmunotherapy in patients with transformed diffuse large B-cell lymphoma
Tamer Othman,1 Paul Frankel,2 Pamela Allen,3 Leslie L. Popplewell,1 Geoffrey Shouse,1 Tanya Siddiqi,1 Alexey V. Danilov,1 Nora Ruel,2 Shari Daniels,1 Lacolle Peters,1 Stella Khoo,1 Steven T. Rosen,1 Elad Sharon,4 Miguel Villalona-Calero,5 Christopher Ruel,2 Joseph Tuscano6 and Alex F. Herrera1
1Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA; 2Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA; 3Winship Cancer Institute at Emory University, Decatur, GA; 4Division of Cancer Treatment and Diagnosis, National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD; 5Department of Medical Oncology & Therapeutics Research, City of Hope National Cancer Center, Duarte, CA and 6Department of Internal Medicine, Division of Malignant Hematology, Cellular Therapy and Transplantation, University of California Davis School of Medicine, Sacramento, CA, USA
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 eval- uation 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.
Introduction
Patients with chronic lymphocytic leukemia/small lympho- cytic lymphoma and indolent B-cell non-Hodgkin lympho- mas, including follicular lymphoma (FL), can experience histological transformation to diffuse large B-cell lymphoma (DLBCL). Transformed DLBCL can be challenging to man- age, especially if patients develop relapsed/refractory (R/R) disease.1,2 Patients with R/R transformed DLBCL have a poor prognosis, with an estimated 4-year event free survival and overall survival of 27% and 39%, respectively.3 Standard
therapy for patients with R/R DLBCL who have primary refractory disease or relapse within 12 months after initial anthracycline-based chemoimmunotherapy is to proceed to chimeric antigen receptor (CAR) T-cell therapy, while for those who relapse after more than 12 months the standard management is salvage chemoimmunotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) in chemosensitive patients eligible for transplant, or palliative therapies in patients who are not candidates for transplan- tation.4-6 Among patients with R/R transformed DLBCL, a minority of patients who undergo autologous HSCT or re-
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Correspondence: A.F. Herrera aherrera@coh.org
Received: Accepted: Early view:
January 29, 2024. July 10, 2024. July 18, 2024.
https://doi.org/10.3324/haematol.2024.285185
©2025 Ferrata Storti Foundation Published under a CC BY-NC license