Magrolimab in Combination with Rituximab + Chemotherapy in Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Background Despite recent advances in therapy options, treatment outcomes remain limited in patients with R/R DLBCL. Magrolimab is a first-in-class monoclonal antibody that blocks CD47, a "don't eat me" signal overexpressed on tumor cells, resulting in macrophage-mediated phagocytosis. Magrolimab in combination with rituximab (M+R) demonstrated encouraging safety and efficacy in patients with R/R DLBCL. We report preliminary results from the phase 1b study of M+R + gemcitabine and oxaliplatin (M+R-GemOx) in R/R DLBCL (NCT02953509). Methods Patients eligible for the M+R-GemOx phase 1b cohort had de novo or transformed R/R DLBCL and were ineligible for intensive chemotherapy or autologous stem cell transplant (ASCT) or had relapsed after ASCT. Patients must have received at least 1 prior line of therapy and no more than 3, including prior anti-CD20 therapy. Magrolimab was administered intravenously (IV) at 1 mg/kg at an initial priming dose on day (D) 1, followed by a weekly dose of either 30 mg/kg (n=26) or 45 mg/kg (n=7) (cycles 1 and 2) followed by every-2-week maintenance dose (cycles ≥3) with R-GemOx. Rituximab 375 mg/m2 was administered IV weekly during the first cycle starting with D8, monthly on D1 (cycles 2-6), and every other cycle (cycle ≥8). Gem 1000 mg/m2 and Ox 100 mg/m2 were both administered IV D11 and D23 (cycle 1) and D2 and D15 (cycles 2-4); dosing was permitted beyond cycle 4, per investigator discretion, for a total of 8 doses. Primary endpoints included safety, tolerability, and objective response rate (ORR) per the Lugano criteria as assessed by investigator. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results As of February 28, 2022, 33 patients were treated with M+R-GemOx. The majority were male (63.6%) with an Eastern Cooperative Oncology Group performance status of 0 or 1 (94%) and a median age of 71.0 (range, 31-86) years. Patients had either de novo (n=26) or transformed (n=7) DLBCL; 1 patient had double hit lymphoma. Patients had received a median of 2 (range, 1-7) prior anticancer therapies; 39.4% of patients had disease that was refractory to rituximab, and 42.4% of patients had disease that was refractory to last therapy. Six patients (18.2%) received prior ASCT. The mean (range) numbers of infusions were 16.2 (1.0-48.0), 7.3 (1.0-17.0), 4.4 (1.0-8.0), and 4.4 (1.0-8.0) for M, R, Gem, and Ox, respectively. The most common treatment-emergent adverse events (TEAEs) of any grade were anemia (69.7%; grade ≥3, 60.6%), thrombocytopenia (45.5% grade ≥3, 42.4%), and neutropenia (18.2%; all grade ≥3). Most high-grade TEAEs occurred within the first 12 weeks of therapy. Treatment-related TEAEs leading to magrolimab discontinuation were observed in 6.1% of patients. After a median follow-up of 11.3 (range, 0.1-33.4) months, the ORR and complete response (CR) rate were 51.5% and 39.4%, respectively. Median DOR and time to response (TTR) were 18.0 months (95% CI, 4.7 months to not estimable) and 1.9 (range, 1.8-3.4) months, respectively. Additional efficacy outcomes are presented in Panel 1. Conclusions The tolerable safety profile and promising efficacy of M+R-GemOx, with deep and durable responses and median OS not reached, in patients with R/R DLBCL compares favorably with current standard-of-care regimens. M+R-GemOx also has the potential added advantage of outpatient delivery. This study supports further evaluation of magrolimab combinations for patients with lymphoma. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal