These results indicate the combination’s long-term effectiveness in a population with limited treatment options.
In patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for salvage therapies, magrolimab (Gilead Sciences) plus rituximab (M + R) in combination with gemcitabine-oxaliplatin chemotherapy (GemOx) was well-tolerated and induced modest responses, according to the authors of a study published in Blood Advances.1
At present, there is an unmet need of therapies for patients in the R/R DLBCL setting. For this reason, novel agents are the preferred route for R/R DLBCL; particularly, incorporating newer agents into the existing rituximab-chemotherapy backbone, which may improve treatment responses and patient outcomes.1
Magrolimab, a monoclonal antibody designed to block CD47, reveals prophagocytic signals that are expressed by tumor cells. It also has demonstrated synergy with rituximab in a non-Hodgkin lymphoma (NHL) model, which the authors noted was an important step. Previous phase 1b/2 clinical trial results demonstrated the M + R combination was well-tolerated and showed positive rates of activity in patients with NHL and DLBCL.1,2
In the phase 1b/2 portion of the trial conducted by Advani et al, the overall objective response rate (ORR) was 50% and the complete response (CR) rate was 36%% across 22 patients with DLBCL. For patients with R/R DLBCL (n = 15), ORR was 40% and CR was 33%, with a median follow-up of 6.2 months. Given this short follow-up, the current investigators sought to assess the long-term efficacy and safety of M + R and GemOx in patients with R/R DLBCL (NCT02953509).1,2,3
Patients were treated with either M + R (n = 99) or M + R-GemOx (n = 33). Across both treatment groups (M + R, 99.0%; M + R-GemOx, 60.6%), almost all participants experienced at least 1 any-grade treatment-emergent adverse event (TEAE), with anemia being the most common.1
Regarding efficacy, investigators observed a response in the overall populations and in multiple high-risk subgroups across both treatment groups. In the M + R only group, ORR was 24.2% and 12 patients (12.1%) reached a complete response at a median follow-up of 7.9 months. Median duration of response (DOR) was 9.3 months (95% CI, 3.7-30.9), and the 12-month overall survival (OS) rate was 44.4% (95% CI, 33.6-54.5%).1
Trial Name: Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
ClinicalTrials.gov: NCT02953509
Sponsor: Gilead Sciences
Completion Date: March 25, 2024
Efficacy measurements were higher in the M + R-GemOx cohort, according to the investigators. ORR was 51.5%, with 13 individuals (39.4%) achieving a CR at median follow-up of 11.3 months. Importantly, the 12-month DOR rate was 66.6% (95% CI, 33.1%-86.1%) and the 12-month OS rate was 67.1% (95% CI, 47.5%-80.8%). Data from each cohort indicated long-term efficacy involving the M + R combination.1
These results follow the positive data from the phase 1b portion of the trial, showing that M + R continued to be tolerated in a 3-year follow-up with no novel safety signals seen. Additionally, these initial results demonstrate the tolerability of M + R-GemOx, indicating its potential as a new treatment option for patients in the R/R setting.1,2
Subgroup analysis revealed observable responses even in high-risk and hard-to-treat groups, such as patients aged 75 or older. The investigators recognize in their discussion that the efficacy results they report for M + R-GemOx is lower than those that have been previously reported. However, they note that the treatments have not been compared in a head-to-head, randomized study, though “the totality of the data” backs up the potential of CD47-based therapies in DLBCL.1
“In the rapidly changing landscape of therapies for R/R DLBCL, the optimal role of CD47 blockade remains to be determined,” the study authors wrote. “Additional studies are needed to identify synergistic combinations and predictors of response.”1
