Efficacy of motixafortide plus G-CSF versus plerixafor plus G-CSF for stem cell mobilization and collection in multiple myeloma: A single-center comparative analysis and interim Results from a prospective study in poor mobilizers Free

Introduction Stem cell collection after 4–8 cycles of induction therapy remains standard for multiple myeloma (MM), supporting autologous stem cell rescue/transplantation (ASCT) following high-dose melphalan. The recent growth of cell therapy and CAR-T programs has increased pressure on apheresis capacity, heightening the need for efficient mobilization—particularly for patients with prior drug exposure known to compromise stem cell yield.

Motixafortide, a long-acting CXCR4 inhibitor (≥72 hours receptor occupancy vs. plerixafor's 6–12 hours), was FDA-approved in 2023 for use with G-CSF in MM mobilization. However, no head-to-head comparison with plerixafor has been published. At our institution, a real-world analysis (30 MM patients per cohort) compared G-CSF plus motixafortide (prospectively) against G-CSF plus plerixafor (retrospectively, matched by age, gender, race, and IMiD/daratumumab exposure). There were no significant differences in overall mobilization, collection, or apheresis outcomes. Subgroup analysis suggested that patients with low peripheral blood CD34+ counts (pbCD34 ≤ 5/μL on Day 4 of G-CSF) may achieve a greater rise in CD34+ counts after motixafortide, raising the hypothesis that it may benefit “poor mobilizers.”

We initiated a prospective study to characterize motixafortide efficacy in poor mobilizers (defined as pbCD34+ ≤ 2/μL after 4 days of G-CSF). This interim analysis compares prospective outcomes with motixafortide to a contemporary plerixafor-treated comparator group.

Methods Cohorts in the real-world analysis were matched by demographics and prior drugs (n=30 each). Primary outcomes were number of apheresis/collection days, session duration, and adverse reactions requiring medical intervention. For the prospective poor mobilizer study, motixafortide was selectively administered to MM patients (n=9, target n=20) meeting the strict pbCD34+ ≤ 2/μL criterion after 4 G-CSF days. A contemporaneous comparator group of 36 similar MM patients treated with plerixafor was identified retrospectively by the same criterion. Outcomes included fold-increase in pbCD34+ (pre-injection vs. pre-apheresis), total CD34+ collection yield, and safety. Statistical analysis used the Mann-Whitney and Student's t-test (p < 0.05).

Results In the initial real-world comparison, G-CSF plus motixafortide and G-CSF plus plerixafor were associated with similar increases in pbCD34+, CD34+ yield, apheresis duration, and collection efficiency. Among poor mobilizers (Day 4 CD34+≤ 5/μL), there was a trend toward higher fold-increase with motixafortide, limited by sample size.

In our prospective poor mobilizer cohort (n=9 motixafortide, n=36 plerixafor), motixafortide plus G-CSF produced a significantly greater fold-increase in pbCD34+ (21.6 vs 9.1, p = 6.8 x 10^-4) and higher median Day 1 CD34+ yield (4.12 vs 2.09 million CD34+ cells/kg, p = 5.5 x 10^-4). Patients receiving motixafortide generally reached collection targets faster.

However, adverse reactions were frequent with motixafortide: seven of nine had significant injection site pain, with nearly half requiring intravenous medications or hospitalization for management. Symptoms typically improved within 24h and no life-threatening events were observed.

Conclusions Our prior single-institution real-world comparative analysis did not demonstrate a significant overall benefit of motixafortide compared to plerixafor for unselected MM patients undergoing stem cell mobilization and collection. However, this interim analysis of our ongoing prospective study of “poor mobilizers” suggests that motixafortide may be more efficacious than plerixafor in this subgroup of patients based on fold-increase in pCD34, median stem cells collected in the first day of apheresis, and overall apheresis chair days required to target. Importantly, motixafortide use was associated with a higher frequency and persistence of adverse reactions. Additional data and further demographic matching (i.e., race, previous drug exposure) are under collection to better elucidate motixafortide's efficacy in this population. Full analysis including individual apheresis yields and total collection outcomes is in process. These data will inform future risk-benefit assessments of motixafortide use and help optimize treatment regimens in MM patients who mobilize poorly to initial G-CSF doses.