| Autor: |
Othman T; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Frankel P; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA., Allen P; Winship Cancer Institute at Emory University, Decatur, GA., Popplewell LL; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Shouse G; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Siddiqi T; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Danilov AV; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Ruel N; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA., Daniels S; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Peters L; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Khoo S; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Rosen ST; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA., Sharon E; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD., Villalona-Calero M; Department of Medical Oncology and Therapeutics Research, City of Hope National Cancer Center, Duarte, CA., Ruel C; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, CA., Tuscano J; Department of Internal Medicine, Division of Malignant Hematology, Cellular Therapy and Transplantation, University of California Davis School of Medicine, Sacramento, CA., Herrera AF; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA. aherrera@coh.org. |
| Abstrakt: |
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. |
