Steady-state mobilization with on-demand plerixafor after CD38 antibody-based induction in multiple myeloma patients

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for fit patients with newly diagnosed multiple myeloma (MM). The increasing use of CD38 antibody-based quadruplet induction regimens such as daratumumab-VTd (Dara-VTd) has raised concerns regarding impaired stem cell mobilization.

We conducted a retrospective single-center analysis comparing steady-state stem cell mobilization after Dara-VTd versus bortezomib-cyclophosphamide-dexamethasone (VCd) induction. Mobilization kinetics, plerixafor use, and CD34⁺ collection outcomes were evaluated. CD34⁺ counts prior to first apheresis were adjusted for plerixafor use (adjCD34⁺). Multivariate logistic regression was performed to identify predictors of mobilization success.

Among 153 patients, 85 received Dara-VTd and 68 received VCd. Despite significantly deeper responses after Dara-VTd (≥VGPR 81% vs. 42%; p < .01), these patients showed lower adjCD34⁺ counts prior to first apheresis (16 vs. 50/μL; p < .01) and required plerixafor more frequently (64% vs. 15%; p < .01). Nevertheless, cumulative CD34⁺ yields were comparable between Dara-VTd and VCd (6.4 vs. 6.0 × 10⁶ CD34⁺ cells/kg; p = .15), and target yields were achieved in the majority of patients proceeding to apheresis (90% vs. 94%). Dara-VTd induction, prior radiation, and high tumor burden were identified as independent negative predictors of mobilization success.

Although Dara-VTd induction is associated with impaired mobilization kinetics, successful steady-state mobilization remains feasible. On-demand plerixafor use overcomes mobilization deficits, supporting this approach in patients receiving CD38-based quadruplet induction therapy. Furthermore, follow-up analysis of stem cell graft utilization demonstrates a high proportion of collected but unused stem cell grafts in both cohorts.