In the battle against multiple myeloma (MM), T cell strategies have emerged as crucial, exploiting their natural tumor-cell targeting ability to enhance patient outcomes.Recent studies underscore the dual roles of T cells in MM: while specific T cells can effectively target and destroy MM cells, regulatory T cells may block this response, highlighting the complexity of the immune environment in MM [1,2].Elotuzumab, targeting the SLAM family member 7 (SLAMF7) protein, represents a promising advance enhancing natural killer (NK) cell activity against MM cells modulating T cell responses.This antibody not only boosts NK cell-mediated destruction of MM cells but also affects T cells, including a specific regulatory CD8 + subset, further contributing to its immunomodulatory effects [3][4][5].Despite these promising mechanisms, clinical trials including the German-Speaking Myeloma Multicenter Group (GMMG)-HD6 study have yielded mixed results, highlighting the need for further investigation into its role in MM treatment [6][7][8][9][10].This study aims to delve deeper into the impact of elotuzumab on T cell subsets within the MM microenvironment to elucidate its prognostic implications and refine therapeutic strategies.Within the context of the GMMG-HD6 trial, we performed a planned subgroup-analysis on SLAMF7 high expressing T cell subsets.The GMMG-HD6 trial assessed elotuzumab combined with lenalidomide, bortezomib, dexamethasone (RVd) in newly diagnosed MM patients.Participants were allocated into four groups: RVd/R (RVd induction/consolidation plus lenalidomide maintenance), RVd/Elo-R (RVd induction, elotuzumab+RVd consolidation, and elotuzumab+lenalidomide maintenance), Elo-RVd/R (elotuzumab+RVd induction, RVd consolidation, lenalidomide maintenance), and Elo-RVd/Elo-R (elotuzumab+RVd for both induction/consolidation and elotuzumab+lenalidomide maintenance).Following induction, all underwent stem cell mobilization, high-dose melphalan, autologous stem cell transplantation, and two consolidation cycles, with 26 cycles of maintenance over three years (Fig. 1A).564 patients were initially randomized in the trial.Five patients were excluded from the study due to violation of major eligibility criteria.The intention-to-treat (ITT) population of the study consisted of 559 patients.Peripheral blood (PB) samples for immune cell analysis were collected at baseline (T1)

CD8+ CD28− regulatory T cells after induction therapy predict progression-free survival in myeloma patients: results from the GMMG-HD6 multicenter phase III study