The PRIME study is a prospective, multicenter, non-interventional exploratory study investigating immune fitness in patients aged 65 years or older with relapsed or refractory multiple myeloma treated with standard-of-care CAR-T cell therapy or bispecific antibodies.
The study is based on the hypothesis that chronological age and clinical frailty do not fully explain the variability in efficacy and toxicity observed with T-cell-directed immunotherapies. Baseline peripheral blood samples will be collected before treatment initiation for comprehensive immune profiling using multiparametric flow cytometry. The analysis will characterize T-cell differentiation, activation, senescence, exhaustion, regulatory T cells, and T-helper cell subsets through the evaluation of markers including CD3, CD4, CD8, CD25, CD27, CD28, CD38, CD45, CD45RO, CD57, CD127, KLRG1, PD-1, TIM-3, LAG-3, TIGIT, CCR4, CCR6, and CXCR3. Serum samples will also be collected to measure soluble B-cell maturation antigen (sBCMA) and senescence-associated soluble biomarkers.
Participants will be followed according to routine clinical practice. Clinical data collected during follow-up will include disease characteristics, geriatric assessment, sarcopenia assessment, treatment response, and treatment-related toxicities. The primary objective is to evaluate the association between baseline immune fitness and treatment response at 3 months. Secondary analyses will investigate the relationship between immune profiles and adverse events, geriatric status, and sarcopenia. The results are expected to improve understanding of the biological determinants of response and toxicity to T-cell-directed immunotherapies and to support improved risk stratification in older patients with relapsed or refractory multiple myeloma.
