Mecapegfilgrastim for prophylaxis of immunochemotherapy-induced neutropenia in patients with diffuse large B-cell lymphoma: A multicenter pilot trial

Abstract Introduction: R-CHOP is the current standard first-line treatment for diffuse large B-cell lymphoma (DLBCL). Chemotherapy-induced neutropenia (CIN) is a common and severe complication in these patients. Mecapegfilgrastim is a long-acting pegylated recombinant human G-CSF (PEG-rhG-CSF) and a biosimilar of pegfilgrastim.This study evaluated the efficacy and safety of mecapegfilgrastim in preventing CIN in treatment-naive patients with diffuse large B-cell lymphoma (DLBCL).Methods: In this open-label, multicenter, controlled exploratory trial (NO. ChiCTR2100048196), DLBCL patients aged 18-75 years without prior systemic chemotherapy were randomly assigned (2:1) to receive mecapegfilgrastim (6 mg, 24-48 hours post-chemotherapy) or no prophylactic intervention. Both groups received 4 cycles of R-CHOP or R-CHOP-like chemotherapy. Recombinant human G-CSF (rhG-CSF) was administered when neutrophil counts fell below 0.5×109/L in the mecapegfilgrastim group and below 1.0×109/L in the control group. The primary endpoint was the incidence of grade ≥3 neutropenia (absolute neutrophil count <1.0×109/L) during cycle 1.Results: From October 2021 to June 2024, 42 patients were enrolled. In the mecapegfilgrastim group, 28 patients were included, with a median age of 58 years (range: 33-75 years), and 13 patients (46.4%) were male. In the control group, 14 patients were included, with a median age of 46 years (range: 26-74 years), and six patients (42.9%) were male. The baseline ANC in the mecapegfilgrastim group was 4.20 ± 2.8×109/L, compared to 4.39 ± 2.3×109/L in the control group. White blood cell counts, hemoglobin levels, and platelet counts were comparable between the two groups. During cycle 1, the grade ≥3 neutropenia rate was 32.14% (95% CI, 15.88 to 52.35) in the mecapegfilgrastim group versus 64.29% (95% CI, 35.14 to 87.24) in the control group (difference: -32.14%; 95% CI, -58.23 to -0.01; nominal P=0.096). Across cycles 2–4 and overall (cycles 1–4), the mecapegfilgrastim group consistently showed lower grade ≥3 neutropenia rates (differences: -29.77%, -40.45%, -48.99%, and -57.14%, respectively; nominal P<0.05, except for cycle 2). Mean nadir neutrophil counts were higher in the mecapegfilgrastim group across all cycles (nominal P<0.05). No cases of febrile neutropenia occurred in the mecapegfilgrastim group, compared to one case in the control group. Short-acting G-CSF use was lower in the mecapegfilgrastim group across all cycles (nominal P<0.05, except for cycle 3). The objective response rate (ORR) was 75.0% (95% CI, 55.1 to 89.3) in the mecapegfilgrastim group and 57.1% (95% CI, 28.9 to 82.3) in the control group (nominal P=0.298). Grade ≥3 neutropenia rates were lower in the mecapegfilgrastim group among ORR achievers and non-achievers (nominal P values: 0.0352 and 0.0210, respectively). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 42.9% of the mecapegfilgrastim group and 92.9% of controls; serious TEAEs were reported in 7.1% of patients in both groups.Conclusion: This study is the first to demonstrate that the long-acting G-CSF, mecapegfilgrastim, exhibits a favorable safety profile and effectively reduced the incidence and severity of CIN in DLBCL patients receiving R-CHOP or R-CHOP-like regimens. These findings support its potential as a prophylactic option in this population, warranting further investigation in large-scale randomized trials.