Etoposide-cytarabine-pegfilgrastim (EAP) and disease-specific chemotherapy regimens for hematopoietic stem cell mobilization in lymphoma: A randomized phase III trial

Abstract

Abstract Background: Enough hematopoietic stem cell (HSC) collection is essential for successful autologous stem cell transplantation (auto-SCT) for lymphoma patients. The effectiveness of collection is greatly impacted by mobilization tactics, however the best approaches are still up for debate. Conventional treatments, like chemotherapy tailored to a particular disease, are frequently employed but have poor mobilizing effectiveness. The EAP regimen (etoposide, cytarabine, and pegfilgrastim) may be a promising alternate mobilization methodology that could get beyond the drawbacks of traditional methods, according to recent phase II results. Aims: For the purpose of mobilizing hematopoietic stem cells (HSCs) in patients with non-Hodgkin lymphoma (NHL), this multicenter, randomized, phase III research (NCT06520163) contrasted the EAP regimen with a disease-specific chemotherapy regimen. Methods: The trial assessed the efficacy and safety of the EAP regimen (etoposide 75 mg/m²/day + cytarabine 200 mg/m² every 12 hours on days 1–2, followed by pegfilgrastim 6 mg on day 6) versus a disease-specific chemotherapy regimen (control) for HSC mobilization in adults with NHL. Patients were stratified by baseline platelet count (>150×10⁹/L vs. ≤150×10⁹/L) and then randomized in a 2:1 ratio to EAP or control. The primary endpoint was the proportion of patients achieving the optimal CD34+ cell collection target (≥5×10⁶/kg) after one apheresis session. Secondary endpoints included: (1) rates of achieving the minimum target (≥2×10⁶ CD34+ cells/kg) and optimal target (≥5×10⁶ CD34+ cells/kg) mobilization; (2) median cumulative CD34+ cell yield; (3) mean number of apheresis sessions required; (4) safety profiles, encompassing adverse event frequency and severity; and (5) rates of plerixafor utilization between the groups. Results: Between July 2024 and July 2025, 44 patients from 10 sites were randomized to either EAP (n = 30) or control (n = 14). Age, gender, ECOG, and platelet count were all balanced at baseline.Significantly more EAP patients (73.3% [22/30]) than control (28.6% [4/14]; p=0.005) reached the optimal collection threshold following one apheresis session. EAP was preferred by trends for achieving the optimal yield (80.0% [24/30] vs. 50.0% [7/14]; p=0.074) and target yield (≥2×10⁶ CD34+ cells/kg: 96.7% [29/30] vs. 78.6% [11/14]; p=0.088).EAP produced a higher median cumulative CD34+ collection (9.3×10⁶/kg vs. 5.7×10⁶/kg; p=0.121) and needed fewer mean apheresis sessions (1.2 vs. 1.5; p=0.095). Thrombocytopenia and neutropenia/infections safety profiles were similar (p>0.5). Significantly more plerixa was needed for rescue by the control group (35.7% [5/14] vs. 6.7% [2/30]; p=0.025). Conclusion:In fewer apheresis sessions, more patients were able to reach ideal HSC collection thresholds thanks to the EAP regimen's improved mobilization effectiveness and comparable safety. Given the markedly decreased demand for plerixa for rescue, EAP appears to be a financially sensible mobilizing technique for NHL patients.