Atezolizumab combined with immunogenic salvage chemoimmunotherapy in patients with transformed diffuse large B-cell lymphoma
Tamer Othman,
Paul Frankel,
Pamela Allen,
Leslie L. Popplewell,
Geoffrey Shouse,
Tanya Siddiqi,
Alexey V. Danilov,
Nora Ruel,
Shari Daniels,
Lacolle Peters,
Stella Khoo,
Steven T. Rosen,
Elad Sharon,
Miguel Villalona-Calero,
Christopher Ruel,
Joseph Tuscano,
Alex F. Herrera
Affiliations
Tamer Othman
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Paul Frankel
Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA
Pamela Allen
Winship Cancer Institute at Emory University, Decatur, GA
Leslie L. Popplewell
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Geoffrey Shouse
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Tanya Siddiqi
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Alexey V. Danilov
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Nora Ruel
Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA
Shari Daniels
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Lacolle Peters
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Stella Khoo
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Steven T. Rosen
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Elad Sharon
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD
Miguel Villalona-Calero
Department of Medical Oncology and Therapeutics Research, City of Hope National Cancer Center, Duarte, CA
Christopher Ruel
Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA
Joseph Tuscano
Department of Internal Medicine, Division of Malignant Hematology, Cellular Therapy and Transplantation, University of California Davis School of Medicine, Sacramento, CA
Alex F. Herrera
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
Patients with relapsed/refractory (R/R) transformed diffuse large B-cell lymphoma (DLBCL) from indolent B-cell lymphomas, including Richter transformation (RT), have a poor prognosis. PD-1/PD-L1 antibodies produce modest objective and complete response rates (ORR and CRR) in B-NHL as monotherapy but may synergize with immunogenic chemotherapies like 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 RT. We conducted a phase I trial including patients with transformed DLBCL after ≥1 prior therapy. Patients received up to 4 cycles of R-GemOx-+Atezo. Patients in CR could then proceed to Ratezo maintenance until progression. A safety lead-in with dose-limiting toxicity (DLT) evaluation was enrolled to confirm the recommended phase 2 dose (RP2D), followed by 2 expansion cohorts: one for transformed follicular lymphoma (FL) and another for non-FL transformed DLBCL, including RT. Twenty-seven patients were enrolled. One of the 6 safety lead-in patients had a DLT attributed to atezolizumab, a grade 4 Stevens-Johnson syndrome (SJS). The most common grade ≥3 events were neutropenia (18.5%), lymphopenia (18.5%), and thrombocytopenia (14.8%). The overall and complete response rates (ORR and CRR) were 59% and 33%, respectively. The ORR and CRR in transformed FL were 79% and 43%, and 38% and 23% in transformed non-FL, respectively. The median PFS and OS 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 R/R transformed DLBCL.
