Pre-Transplant Marrow CD3+ T cell Status and Outcomes in Newly Diagnosed Multiple Myeloma Undergoing Autologous Hematopoietic Cell Transplantation

T cells are key components of the adaptive immune system and play a critical role in tumor control and long-term cure. They can recognize and eliminate tumor cells directly or indirectly through cytokine release and Fas/FasL-mediated apoptosis. Recent advances in multiple myeloma (MM) treatment involving T cell–redirecting therapies such as bispecific antibodies and CAR-T cells have greatly improved outcomes, highlighting the importance of T-cell functionality. Given this, it remains unclear whether the baseline T-cell repertoire, particularly marrow CD3+ T-cell content, influences outcomes in newly diagnosed MM (NDMM) patients undergoing autologous hematopoietic cell transplantation (Auto-HCT). To evaluate whether pre-transplant marrow CD3⁺ T-cell levels are associated with post-transplant outcomes, including progression-free survival (PFS) and overall survival (OS), in NDMM patients undergoing Auto-HCT. We performed a retrospective single-institution study of 180 NDMM patients who underwent Auto-HCT between 2019–2024. Disease stage, cytogenetic risk, and depth of response before transplant (PR, VGPR, CR) were recorded, with post-transplant responses assessed at day +100. Flow cytometry of pre-transplant marrow quantified CD3+ T cells, using the median count of 440 as the cutoff for CD3-high (>440) and CD3-low (<440). Survival outcomes were analyzed using Kaplan–Meier and Cox proportional hazards models. Among 180 patients, the median age was 61.5 years (range 35.8–76.5), and 61.7% were male. Myeloma subtypes included IgG (61.7%), IgA (21.7%), and FLC (12.2%). Median OS was reached only in CD3-high Stage I (73 months). While the log-rank test showed no significant OS difference ( p =0.18), the Gehan–Breslow–Wilcoxon test ( p =0.009) suggested an early survival advantage in CD3-low patients. Median PFS was 52 months in CD3-low Stage I, not reached in Stage II, and 34 months in Stage III (log-rank p =0.17). For CD3-high patients, PFS was not reached in Stage I, 41 months in Stage II, and 35 months in Stage III. When analyzed by CD3 status alone, median PFS was not reached for CD3 <440 and was 57 months for CD3 >440 (HR 0.67; 95% CI 0.40–1.13; log-rank p =0.13). Pre-transplant marrow CD3+ T-cell levels did not significantly affect PFS or OS following Auto-HCT, though an early survival signal was observed among CD3-high patients. Further prospective studies exploring additional T-cell subsets (CD4, CD8) and their relationship with CD3 levels are warranted to clarify how immune repertoire diversity impacts post-transplant outcomes in NDMM.