Transplantation and cellular therapy · 2025
The Impact of Anti-CD38 Monoclonal Antibody Therapy on Stem-Cell Mobilization Yields in Patients With Newly Diagnosed Multiple Myeloma (NDMM) Referred From Community and Academic Oncology Practices: Single Center, Real World Data 2021-2024.
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Uzun Dilek, Paul Jeddeo Michael, Jensen Alexandria, Tamaresis John, Domingo Walter, Arai Sally, Ventura Felipe Araya, Rocha Jennifer, Bennett Leslie, Jones Amelia, Bharadwaj Sushma, Johnston Laura, Lowsky Robert, Rezvani Andrew, Shiraz Parveen, Shizuru Judith, Weng Wen-Kai, Hosoya Hitomi, Sidana Surbhi, Miklos David, Muffly Lori, Mikkilineni Lekha
Аннотация
BACKGROUND: Autologous stem cell transplantation (ASCT) remains a standard component of frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). CD38 monoclonal antibodies (mAbs), such as daratumumab and isatuximab, have been incorporated into induction regimens and are associated with deeper responses. However, their impact on hematopoietic stem cell mobilization is unclear, particularly in real-world practice.
OBJECTIVES: We aimed to evaluate the impact of CD38 monoclonal antibody (mAb)-based induction on total stem cell yield in newly diagnosed multiple myeloma (NDMM) patients undergoing autologous stem cell transplantation (ASCT), hypothesizing that CD38 mAb exposure would reduce mobilization efficiency. Secondary objectives included examining plerixafor use, apheresis session numbers, and modeled cost differences.
STUDY DESIGN: This retrospective, single-center analysis included 375 NDMM patients treated between 2021 and 2024. Patients received either CD38 mAb-containing triplet/quadruplet induction or non-CD38-based triplet therapy, followed by stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) with and without plerixafor. Mobilization goal was defined as 2 × 10⁶ CD34⁺ cells/kg for primary transplant and 2 × 10⁶ CD34⁺ cells/kg for a backup stem cell product (per institutional guidelines). Multivariable linear regression assessed independent predictors of stem cell yield. A cost analysis estimated per-patient mobilization expenses.
RESULTS: CD38 mAb exposure was associated with lower, though clinically comparable, median stem cell yields (5.2 vs. 5.5 × 10⁶ CD34⁺ cells/kg; P = .001), a greater number of apheresis sessions (median 2 vs. 1; P = .0008), and more frequent plerixafor use (median 2 vs. 1 dose; P = .0003). In multivariable analysis, CD38 mAb exposure was associated with a 9.4% reduction in average stem cell yield (95% CI, 1.7%-16.5%; P = .019), while each additional week of post-induction washout was associated with a 3.4% increase in yield (95% CI, 0.7%-6.2%; P = .015). Modeled mobilization costs were $23,285 higher in the CD38-exposed group.
CONCLUSION: CD38 mAb-containing induction regimens were associated with inferior stem cell mobilization yields and higher resource utilization. Extended washout periods modestly improved yield, highlighting a potential modifiable factor. These findings support the need for tailored mobilization strategies in CD38 mAb-exposed patients and warrant prospective evaluation of alternative mobilization agents and collection protocols to optimize efficiency and cost-effectiveness in the ASCT setting.
OBJECTIVES: We aimed to evaluate the impact of CD38 monoclonal antibody (mAb)-based induction on total stem cell yield in newly diagnosed multiple myeloma (NDMM) patients undergoing autologous stem cell transplantation (ASCT), hypothesizing that CD38 mAb exposure would reduce mobilization efficiency. Secondary objectives included examining plerixafor use, apheresis session numbers, and modeled cost differences.
STUDY DESIGN: This retrospective, single-center analysis included 375 NDMM patients treated between 2021 and 2024. Patients received either CD38 mAb-containing triplet/quadruplet induction or non-CD38-based triplet therapy, followed by stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) with and without plerixafor. Mobilization goal was defined as 2 × 10⁶ CD34⁺ cells/kg for primary transplant and 2 × 10⁶ CD34⁺ cells/kg for a backup stem cell product (per institutional guidelines). Multivariable linear regression assessed independent predictors of stem cell yield. A cost analysis estimated per-patient mobilization expenses.
RESULTS: CD38 mAb exposure was associated with lower, though clinically comparable, median stem cell yields (5.2 vs. 5.5 × 10⁶ CD34⁺ cells/kg; P = .001), a greater number of apheresis sessions (median 2 vs. 1; P = .0008), and more frequent plerixafor use (median 2 vs. 1 dose; P = .0003). In multivariable analysis, CD38 mAb exposure was associated with a 9.4% reduction in average stem cell yield (95% CI, 1.7%-16.5%; P = .019), while each additional week of post-induction washout was associated with a 3.4% increase in yield (95% CI, 0.7%-6.2%; P = .015). Modeled mobilization costs were $23,285 higher in the CD38-exposed group.
CONCLUSION: CD38 mAb-containing induction regimens were associated with inferior stem cell mobilization yields and higher resource utilization. Extended washout periods modestly improved yield, highlighting a potential modifiable factor. These findings support the need for tailored mobilization strategies in CD38 mAb-exposed patients and warrant prospective evaluation of alternative mobilization agents and collection protocols to optimize efficiency and cost-effectiveness in the ASCT setting.