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    MRD and Biomarkers

    Category: MRD and Biomarkers

    Stem cell autograft minimal residual disease negativity predicts improved outcomes after autologous stem cell transplant for multiple myeloma

    (PA-184) Stem Cell Autograft Minimal Residual Disease Negativity Predicts Improved Outcomes After Autologous Stem Cell Transplant for Multiple Myeloma

    Friday, September 19, 2025
    Introduction: Autologous stem cell transplantation (ASCT) remains a standard-of-care for newly diagnosed multiple myeloma (NDMM). Advances in induction regimens have improved rates of bone marrow (BM) minimal residual disease (MRD) negativity and survival. However, the prognostic relevance of MRD status in stem cell autografts (AG) remains unclear.

    Methods: We evaluated 659 NDMM patients who underwent up-front ASCT at our institution between Sept 2027 and Dec 2023, with AG and BM MRD assessments using next-generation flow (NGF). AG MRD was tested at stem cell collection. BM MRD was assessed post-induction/pre-collection and at 3 months post-ASCT. Kaplan-Meier methods, log-rank tests, and Cox models were used to evaluate progression-free survival (PFS) and overall survival (OS) from ASCT.

    Results: Baseline characteristics were comparable between the MRD-negative and positive groups with a median age 63 and 56% male. ISS III and R-ISS III stages were seen in 22% and 33%, respectively; 56% had high-risk cytogenetics. The median number of induction cycles was 6: 55% received lenalidomide/proteasome inhibitor-based triplets (RVd, KRd), 29% daratumumab-based quadruplets (D-RVd, D-KRd), and 26% other regimens. VGPR or better was highest with D-KRd (86.5%), followed by D-RVd (82%), KRd (75.8%), RVd (62.5%), and others (60%). AG MRD-negativity was observed in 72.7% of matched cases, compared to 22% in BM post-induction samples. All MRD-negative BMs had MRD-negative AGs. Among MRD-positive BMs, 65% had MRD-negative AGs, while the remaining 35% had MRD-positive AGs. Importantly, no MRD-negative BMs had MRD-positive AGs. Most patients (95%) received post-ASCT maintenance, primarily single agent lenalidomide. Multi-drug post-ASCT consolidation therapy was more common in the AG MRD-positive group (28% vs. 6.8%). With a median follow-up among survivors of 32 months, AG MRD-negativity was associated with improved PFS (3-year: 76% vs. 50%, log-rank p< 0.002) and OS (3-year: 92% vs. 69%, p< 0.002). This benefit extended across BM MRD and cytogenetic subgroups. At 3 years, OS was 95% in AG-/BM-, 93% in AG-/BM+, and 76% in AG+/BM+. Among high-risk cytogenetics, OS at 3 years was 95% (AG-/HR-), 93% (AG-/HR+), 82% (AG+/HR-), and 72% (AG+/HR+). In univariable analysis, AG MRD-positivity (HR 3.37, 95% CI 2.55 - 5.65), BM MRD-positivity (HR 2.09, 95% CI 2.26 – 3.56), ISS > I, and high-risk cytogenetics were associated with shorter PFS. In multivariable analysis, AG MRD-positivity (HR 2.28, 95% CI 2.57 – 3.25) and ISS > I remained significant. Importantly, AG MRD status retained prognostic impact for both PSF and OS in delayed ASCT recipients (n=78).

    Conclusions: MRD-negativity in autografts is independently associated with superior PFS and OS following ASCT. These findings support AG MRD status as a valuable prognostic marker beyond conventional post-induction BM MRD status, with potential implications for tailoring post-ASCT therapy.