Safety and Efficacy of Etoposide Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Newly Diagnosed Multiple Myeloma

Background: Autologous stem cell transplantation (ASCT) remains the gold standard treatment for eligible multiple myeloma (MM) patients. Successful hematopoietic stem cell (HSC) collection is crucial for optimal post-ASCT outcomes. While granulocyte colony-stimulating factor (G-CSF) alone or combined with cyclophosphamide are standard mobilization strategies, up to 20% of newly diagnosed MM (NDMM) patients fail to collect sufficient HSCs for ASCT. This study evaluates the safety and efficacy of etoposide combined with G-CSF for stem cell mobilization in NDMM patients undergoing ASCT.

Methods: We conducted a retrospective analysis of 22 consecutive NDMM patients who underwent ASCT at our center from January 2022 to May 2024. We assessed disease characteristics (immunoglobulin subtype, ISS and R-ISS staging, cytogenetics, renal impairment, secondary plasma cell leukemia, amyloidosis, extramedullary disease), induction regimens, stem cell mobilization parameters, conditioning protocols, treatment responses per International Myeloma Working Group (IMWG) criteria, and post-transplant complications. Survival analysis was also performed.

Results: The study cohort (n=22) had equal gender distribution with a median age of 54 years (range: 45-63). MM subtypes were IgG (36.3%), IgA (22.7%), and light chain (41%). Advanced disease was common, with 45.5% (n=10) classified as ISS stage III and 9.1% (n=2) as R-ISS stage III. Notably, 36.4% (n=8) presented with renal impairment (median eGFR 10.6 mL/min, range: 4.8-23.9). The cohort included one case each of secondary plasma cell leukemia, light chain amyloidosis, and ISS/R-ISS stage II with t(11;14). Extramedullary disease was observed in 18.2% (n=4) of patients. All patients had low to intermediate hematopoietic cell transplantation-comorbidity index (HCT-CI) scores. The median time from diagnosis to ASCT was 8 months (range: 4-13).

Patients received 4-6 cycles of induction therapy, predominantly VRD (59%), followed by VCD, XVPD, and DKD (9% each), with VTD and liposomal mitoxantrone + VRD (4.5% each) less frequently used. This approach yielded response rates of CR (91%), VGPR (4.5%), and PR (4.5%). Our mobilization protocol, consisting of etoposide (375 mg/m² for 2 days) with G-CSF (10 μg/kg/day, split-dose, for 5 days), was successful in all patients, including four with severe renal impairment (eGFR <30 mL/min). All patients achieved successful mobilization on the first attempt with a single apheresis session. The primary adverse events were grade III-IV bone marrow suppression (100%) and febrile neutropenia (22.7%), with no documented bloodstream infections or hepatorenal toxicity. The median yield of CD34+ and mononuclear cells were 10.8 × 10⁶ cells/kg (range: 2.9-30.0) and 6.0 × 10⁸ cells/kg (range: 4.0-13.1), respectively. Importantly, 77.3% of patients achieved optimal collection, defined as >5 × 10⁶ CD34+ cells/kg. Conditioning consisted of oral melphalan (200 mg/m²), reduced to 140 mg/m² in 4 patients with renal impairment. Post-ASCT complications were predominantly infectious (22.7%) and gastrointestinal (13.6%). For the four patients with renal failure, there was no significant difference between pre-ASCT and post-ASCT eGFR (17.1 ± 4.5 vs. 30.1 ± 16.3 mL/min, P=0.17).

All patients achieved successful engraftment, with median neutrophil and platelet recovery at 13 and 17 days, respectively. The day +100 post-transplant evaluation revealed a CR rate of 90.9%. Maintenance strategies included ixazomib plus dexamethasone (59.1%), lenalidomide (18.2%), ixazomib plus venetoclax (4.5%), while 9.1% received no maintenance. At the time of analysis, median progression-free survival (PFS) and overall survival (OS) had not been reached.

Conclusion: Our findings demonstrate that the combination of etoposide and G-CSF is a highly effective, safe, and cost-efficient mobilization strategy for NDMM patients. This protocol consistently yielded adequate stem cell collections without requiring plerixafor, a costly salvage agent. The exceptional success rate, manageable toxicity profile, and absence of renal function deterioration highlight the potential of this approach. These promising results warrant validation through large-scale, randomized controlled trials to potentially establish this regimen as a new standard in NDMM stem cell mobilization.