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 fatigue (69.7%; grade ≥3, 12.1%), anemia (69.7%; grade ≥3, 60.6%), diarrhea (60.6%; grade ≥3, 6.1%), and nausea (54.5%; grade ≥3, 9.1%). 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.