Safety and Efficacy of Cyclophosphamide With Dual Mecapegfilgrastim and On‐Demand Plerixafor for Salvage Mobilization in Patients With Initial Mobilization Failure: A Retrospective Cohort

ABSTRACT Initial hematopoietic stem cell (HSC) mobilization failure remains a critical barrier to autologous stem cell transplantation (ASCT) in patients with lymphoma or multiple myeloma (MM). This retrospective cohort study (August 2015 to March 2023) evaluated the efficacy, safety, and cost‐effectiveness of a novel salvage regimen—split‐dose cyclophosphamide (CTX: 1.5 g/m 2 for 2 days) + Mecapegfilgrastim (PEG‐rhG‐CSF) + on‐demand plerixafor (PXF)—compared to conventional strategies (CTX + granulocyte colony‐stimulating factor [G‐CSF] or G‐CSF + PXF) in 118 patients with initial mobilization failure. Patients were stratified into three groups: CTX + PEG‐rhG‐CSF + on‐demand PXF ( n = 46), CTX + G‐CSF ( n = 34), and G‐CSF + PXF ( n = 38). The CTX + PEG‐rhG‐CSF + on‐demand PXF group achieved superior mobilization efficacy: median CD34 + cell yield was 9.2 × 10 6 /kg, which is significantly higher than that of CTX + G‐CSF group (4.1 × 10 6 /kg; p < 0.05) and G‐CSF + PXF group (4.6 × 10 6 /kg; p < 0.05). Rates of achieving the thresholds of ≥ 2 × 10 6 CD34 + cells/kg and ≥ 5 × 10 6 CD34 + cells/kg were significantly higher in the CTX + PEG‐rhG‐CSF + on‐demand PXF group. This superior mobilization efficacy also brought fewer apheresis sessions: only 15.2% of patients in the CTX + PEG‐rhG‐CSF + on‐demand PXF cohort required ≥ 2 sessions, compared to 70.5% in CTX + G‐CSF group and 57.9% in G‐CSF + PXF group ( p < 0.001). Safety profiles were comparable across cohorts: febrile neutropenia occurred in 13% of patients in CTX + PEG‐rhG‐CSF + on‐demand PXF group (vs. 26.5% in CTX + G‐CSF; p = 0.33). Severe neutropenia (Grade 3–5) was common in CTX‐containing groups (91.3% vs. 90.2%; p = 0.88) but mostly being transient, with no treatment‐related mortality. Neutrophil engraftment times were similar (median 10–11 days; p = 0.406) in all groups. Cost analysis revealed that the CTX + PEG‐rhG‐CSF + on‐demand PXF regimen was more cost‐effective than G‐CSF + PXF regimen (5511 vs. 8761; p < 0.05) but more expensive than CTX + G‐CSF regimen ($3012; p < 0.05). In conclusion, CTX + PEG‐rhG‐CSF + on‐demand PXF is a highly effective salvage mobilization strategy for patients with initial HSC mobilization failure, yielding higher CD34 + cell counts with fewer aphereses and acceptable safety. With balanced advantages in efficacy, safety, and cost‐effectiveness, the CTX + PEG‐rhG‐CSF + on‐demand PXF regimen can be a preferred salvage option for ASCT candidates with prior mobilization failure.