Atezolizumab, Immunogenic Chemotherapy Combination Shows Promise for DLBCL Treatment

A combination therapy of atezolizumab (tecentriq) with rituximab (Rituxan), gemcitabine (gemzar), and oxaliplatin (eloxatin; GemOx; R-GemOx+Atezo) has demonstrated favorable safety and efficacy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). These findings, published in Haematologica, indicated that those with transformed follicular lymphoma (FL) exhibited the highest response rates.¹ 

Managing R/R-transformed DLBCL remains a challenge, as affected patients have an approximate 27% chance of 4-year event-free survival and a 39% chance of overall survival.²

Patients with R/R transformed DLBCL have modest 4-year event free and overall survival rates under 50%, making disease management a persistent challenge | SuriyaPhoto - stock.adobe.com

Atezolizumab is a monoclonal antibody that works to hinder interactions between programmed death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) receptors, which are overexpressed in a variety of non-Hodgkin lymphomas. Previously, atezolizumab has been safely paired with other agents in R/R DLBCL, such as obinutuzumab (gazyva), tazemetostat (tazverik), and polatuzumab vedotin (polivy). However, response rates were modest at best (16%-25%). Emerging data suggests that coupling immunogenic chemotherapy with anti–PD-L1 antibodies may work synergistically to wipe out those tumor cells that are resistant to PD-L1/PD-1 inhibition.¹

“Transformed DLBCL is an ideal disease in which to evaluate the combination of immunogenic chemotherapy and checkpoint inhibitors given the genomic complexity of transformed FL,” the authors commented. To investigate this further, they launched a pilot study to better evaluate the safety and efficacy of R-GemOx+Atezo in patients with R/R transformed DLBCL, as well as patients with RT.

The multicenter phase 1 trial included centers at Emory University, University of California Davis, and City of Hope. Patients were excluded if they previously received radiotherapy, chemotherapy, systemic immunosuppressive therapy, allogenic hematopoietic stem cell transplantation, an anti-PD-L1/PD-1 therapy, or GemOx.

A total of 27 patients participated in the study. The cohort was aged a median of 68 years; 52% (n = 14) of patients had transformed FL, while the remaining 48% (n = 13) had transformed non-FL. Cases of non-FL included chronic lymphocytic leukemia/small lymphocytic leukemia (n = 9), marginal zone lymphoma (n = 3), and lymphoplasmacytic lymphoma (n = 1).

Throughout the safety evaluation, hypertension (n = 10), vomiting/nausea (n = 12), thrombocytopenia (n = 13), increased transaminase levels (n = 14), and fatigue (n = 15) were the most prevalent adverse events experienced. Neutropenia occurred in 18.5% of patients (n = 5).

Overall response rates registered at a favorable 59% (n = 16), and complete response was achieved for 33% of patients (n = 9). An additional 9 patients (33%) exhibited progressive disease, while 7 (26%) had a partial response, and 1 (4%) had a stable disease.

For patients with FL (n = 14), complete and overall response rates registered at 43% and 79%. These rates were 23% and 38% in patients with non-FL transformed lymphomas, respectfully. Of the patients with RT (n = 9), complete and overall response rates were 11% and 22%, respectfully.

Throughout the entire group, the median overall survival and progression-free survival rates were 7.7 and 3.7 months, respectively. Median progression-free survival was not significantly different between those with transformed non-FL or FL (3.1 vs 3.7 months; P = .4), and the same was true for median overall survival (7.3 vs 22.5 months; P = .4).

“With further validation, the R-GemOx-Atezo regimen could be considered as an option for patients who relapse after CAR T-cell and bispecific antibody therapy,” the authors concluded as they advocated for future efforts to analyze the prognostic value of immunogenic chemotherapy-checkpoint inhibitor combinations for R/R DLBCL.

References

1. Othman T, Frankel P, Allen P, et al. Atezolizumab combined with immunogenic salvage chemoimmunotherapy in patients with transformed diffuse large B-cell lymphoma. Haematologica. 2025;110(1):142-152. doi:10.3324/haematol.2024.285185

2. Kuruvilla J, MacDonald DA, Kouroukis CT, et al. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC CTG LY12. Blood. 2015;126(6):733-8. doi:10.1182/blood-2015-01-622084