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Rituximab, Magrolimab With Chemotherapy Modestly Effective and Well-Tolerated in Patients With R/R DLBCL

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

A staging bone marrow biopsy shows replacement of normal elements by diffuse large B-cell lymphoma, a type of non Hodgkin lymphoma

Image credit: © David A Litman | stock.adobe.com

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

About the Trial

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

REFERENCES
1. Maakaron J, Asch AS, Popplewell L, et al. Magrolimab plus rituximab with/without chemotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2024. doi:10.1182/bloodadvances.2024013338
2. Advani R, Flinn I, Popplewell L, et al. CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin’s lymphoma. N Engl J Med. 2018;379(18):1711-1721. doi:10.1056/NEJMoa1807315
3. ClinicalTrials.gov. Trial of magrolimab (Hu5F9-G4) in combination with rituximab or rituximab + chemotherapy in participants with relapsed/refractory B-cell non-Hodgkin’s lymphoma. National Library of Medicine. Updated May 23, 2024. Accessed September 24, 2024. https://clinicaltrials.gov/study/NCT02953509
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