Magrolimab in Combination With Rituximab in Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma: 3-Year Follow-up Results From a Phase 1/2 Trial

Introduction:
Indolent non-Hodgkin lymphoma (iNHL) is characterized by multiple relapses, with patients experiencing increasingly shorter progression-free intervals. 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. Promising safety and efficacy were previously reported for magrolimab plus rituximab (M+R) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma or iNHL (follicular [FL] or marginal zone [MZL]) in a phase (ph)1b/2 study (NCT02953509). Here we report 3-year follow-up data for M+R in the R/R iNHL cohort.
Methods:
The study enrolled patients with R/R B-cell NHL expressing CD20 by immunohistochemistry or flow cytometry (ph1b) or histologically confirmed iNHL (MZL or FL [grade 1-3a]) that was R/R to ‚â•2 prior lines of therapy (ph2). In ph1b, patients received a magrolimab 1 mg/kg intravenous (IV) priming dose, then 10 mg/kg or 30 mg/kg weekly. In ph2, patients received a magrolimab 1 mg/kg priming dose, then 30 mg/kg (recommended ph2 dose from ph1b) or 45 mg/kg dosing from cycle 2+ until disease progression. In ph1b and ph2, rituximab 375 mg/m was administered IV on days 8, 15, and 22 (cycle 1), day 1 (cycles 2-6), then every other cycle. 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, 46 patients (42 FL, 3 MZL, 1 extranodal MZL) were treated with M+R in ph1b/2. Most patients were male (60.9%), with an Eastern Cooperative Oncology Group performance status of 0-1 (95.7%). Median age was 61.0 (range, 28-87) years. Patients received a median of 3 (range, 1-9) prior therapies; 65.2% had rituximab-refractory disease, and 63.0% had disease refractory to the last treatment regimen. Median duration of magrolimab treatment was 5.3 (range, 0.3-62.3) months, and patients received a mean of 27.8 (range, 2.0-137.0) magrolimab infusions. The most common any-grade treatment-emergent adverse events (TEAEs) were infusion-related reaction (60.9%), headache (52.2%), fatigue (45.7%), cough (45.7%), chills (43.5), and pyrexia (41.3%); TEAEs were predominantly grade 1-2. The most common grade ‚â•3 TEAEs were anemia (21.7%), thrombocytopenia (17.4%), and infusion-related reaction (15.2%). Treatment-related TEAEs led to magrolimab discontinuation in 4.3% of patients. With a median follow-up of 36.7 (range, 1.2-62.3) months, ORR was 52.2%, with 14 patients (30.4%) achieving a complete response. In the 24 patients who achieved a response, the median DOR was 15.9 (95% CI, 5.6 to not estimable) months, with a median time to response of 1.8 (range, 1.6-5.5) months. The median PFS was 7.4 (95% CI, 4.8-13.0) months, and the 2-year PFS rate was 27.4%. The median OS was not estimable, and the 2-year OS rate was 72.5%. Additional safety and efficacy data will be presented.
Discussion:
After 3-year follow-up, M+R continued to be well tolerated, with promising efficacy characterized by deep and durable responses; median OS was not reached in heavily pretreated patients with iNHL. This study supports further evaluation of magrolimab combinations for patients with relapsed FL.