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 P0.05, except for cycle 2). Mean nadir neutrophil counts were higher in the mecapegfilgrastim group across all cycles (nominal P0.05). 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 P0.05, 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.
Li et al. (Mon,) studied this question.