Background:

For multiple myeloma (MM) autologous stem cell transplantation (auto-SCT) to be successful, adequate hematopoietic stem cell (HSC) harvest is essential. Even while mobilization tactics have a big impact on collection results, the best methods are still debatable. Despite their widespread usage, traditional regimens such as cyclophosphamide plus G-CSF (CG) have issues with patient tolerance and constancy of efficacy. Interestingly, new data from a phase II trial indicates that the EAP regimen (etoposide, cytarabine, and pegfilgrastim) shows promise as a different mobilization method.

Aims: The comparative effectiveness and safety of EAP regimen versus CG regimen for HSC mobilization in patients with newly diagnosed MM were evaluated in this multicenter, randomized, phase III controlled trial (NCT06520176).

Methods: Adults with newly diagnosed MM were randomly assigned in a 2:1 ratio to either the experimental (EAP) or control (CG) groups using a stratified block randomization technique. Their previous exposure to lenalidomide (either＞4 cycles or ≤ 4 cycles) determined this allocation.Intravenous etoposide at 75 mg/m² daily, intravenous cytarabine at 200 mg/m² every 12 hours, and subcutaneous pegfilgrastim at 6 mg on day 6 were the therapies administered to patients in the EAP group on days 1 and 2. Granulocyte-coloy stimulating factor (G-CSF) was given subcutaneously starting on day 9 at a dose of 5 µg/kg until the stem cell harvest was finished if the white blood cell count was less than 20,000/μl.On the other hand, patients in the CG group received intravenous cyclophosphamide at a rate of 1–2 g/m² per day on days 1 and 2, as well as subcutaneous G–CSF at a dose of 5 µg/kg from day 6 until the end of the mobilization phase. The percentage of patients who, following a single apheresis session, obtained the optimal collection goal—that is, a yield of CD34+ cells ≥5×10⁶/kg—was the main outcome. Comparing the EAP and CG regimens in a number of important areas was the secondary goal. These included comparing the percentage of patients who cumulatively achieved the target collection value (≥2×10⁶ CD34+ cells/kg) and the ideal collection value; the median cumulative CD34+ cell yield; the average number of apheresis sessions required; the safety profiles of the EAP and CG regimens; and the percentage of patients who required Plerixafor in the EAP and CG groups, respectively.

Results: 71 patients from 11 sites were randomized to be in the EAP (n = 49) or CG (n = 22) groups between July 2024 and July 2025. The baseline factors were evenly distributed across the arms and included age, gender, ECOG performance status, and previous exposure to lenalidomide.After just one apheresis session, 83.7% of patients in the EAP regimen reached the ideal collection threshold, compared to 40.9% in the CG arm (p＜0.0001). This suggests that the EAP regimen has greater mobilization efficiency. In contrast, 100% of EAP patients met the target and 93.9% obtained the ideal yield with just 1.1 mean sessions of apheresis, but only 72.7% of CG patients achieved the target yield (≥2×10⁶ CD34+ cells/kg) and 63.6% achieved the ideal yield, requiring a mean of 1.6 apheresis sessions (p=0.007). The median cumulative output of CD34+ cells in the EAP arm (13.2 ×10⁶/kg, range 2.9–48.9) was notably larger than that of the CG arm (5.5 ×10⁶/kg, range 0–14.6) (p＜0.0001).

In terms of safety, the EAP arm experienced more thrombocytopenia, whereas the CG arm experienced more neutropenia and infections (grade 1-2). 23/49 patients (46.9%) who received EAP experienced grade 4 thrombocytopenia, compared to 3/22 (13.6%) in the CG group (p=0.007). In contrast, 16/49 (32.7%) patients in the EAP arm and 15/22 (68.2%) patients in the CG arm experienced grade 4 neutropenia (p=0.005). The usage of plerixafor rescue was somewhat higher in the CG arm (9.1% vs. 4.1%).

Conclusion:In comparison to CG, EAP showed better mobilization efficiency, with a greater percentage of patients reaching optimal/target HSC collection thresholds in fewer apheresis sessions. There were no unanticipated side effects, and the regimen demonstrated good safety and acceptability. EAP's low plerixafor requirement emphasizes self-sufficiency and establishes it as a good first-line treatment for MM patients, especially in situations with limited resources where access to plerixafor is restricted or prohibitively expensive.

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2025
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