Etoposide +cytarabine plus G-CSF mitigates daratumumab-associated impairment on stem cell mobilization yields in multiple myeloma

Abstract Objective: Quadruplet induction therapy comprising daratumumab(dara) and lenalidomide(lena), followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) has become the standard frontline treatment for patient with multiple myeloma(MM). However, there is concern that dara and lena may impair stem cell mobilization for ASCT. We previously reported the high efficacy of stem cell mobilization using etoposide+cytarabine (EA) plus G-CSF in patients with MM and lymphoma. Here, we evaluated the efficacy and engraftment outcomes of EA plus G-CSF mobilization in MM patients treated with dara-based induction therapy. Methods: This single-center retrospective analysis enrolled 105 MM patients who received dara based (n=37) or lena based (n=68) induction therapy prior to mobilization. All patients were mobilized using EA (etoposide 100 mg/m2, qd d1-3; AraC 0.5 g/m2, q12h d1-3) plus G-CSF (5 µg/kg/day, from d5 until the day of apheresis). Up to two days of apheresis were required in the study. Baseline characteristics showed no significant differences between the groups. Results: The median total CD34+ cells collection was 19.33 × 10⁶/kg in the dara group, significantly lower than that in lena group (25.59 × 10⁶/kg, p=0.005). Notably, patients receiving more than eight doses of dara showed a reduced CD34+ cell collection (median 14.16 × 10⁶/kg vs. 21.45 × 10⁶/kg; p = 0.039). All patients successfully mobilized an adequate number (≥ 2 × 10⁶ cells/kg) of CD34+ cells for ASCT, and the rates of optimal stem cell collection (≥ 5 × 10⁶ CD34+ cells/kg) for a single ASCT were comparable between the two groups (94.6% vs. 94.1%). In the dara group, 89.2% (33/37) of patients achieved at least 10 × 10⁶ CD34⁺ cells/kg, the optimal threshold for tandem ASCT, compared to 92.6% (63/68) in the lena group. Two-day aphereses were required in 45.9% (17/37) of patients in the dara group, more than in the lena group (17.6%, 12/68; p = 0.002). Along with a prolonged duration of grade 4 neutropenia, dara patients experienced more frequent antibiotic usage and longer interval from mobilization to collection (15 vs. 14 days, respectively). The median time to neutrophil recovery post ASCT was delayed in the dara group compared to the lena group (12 vs. 11 days, p = 0.005), while a similar trend was observed for platelet recovery (14 vs. 13 days, p = 0.077). Conclution: Dara impaired stem cell mobilization by reducing CD34+ cell yields and necessitating multiple apheresis sessions to achieve the target yield for ASCT. EA+G-CSF was high efficient to mobilized optimal collection in MM patients treated with dara-based induction therapy, especially for those required tandem ASCT. Key Words：Daratumumab, Etoposide, Cytarabine, Stem cell mobilization, multiple myeloma