Prediction of Response Related to IMmune Age T Cell Fitness in Elderly Patients With Relapsed and Refractory Multiple Myeloma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 31
- 试验地点
- 3
- 主要终点
- Rate of ≥VGPR or better according to IMWG criteria at 3 months.
研究概览
简要总结
Relapsed/refractory multiple myeloma (RRMM) predominantly affects older adults, who exhibit marked heterogeneity in treatment outcomes despite receiving the same therapies. Clinical frailty scores, such as the International Myeloma Working Group (IMWG) Frailty Index, predict survival and treatment tolerance but provide limited information on immune competence, a key determinant of response to T-cell-based immunotherapies.
The PRIME study is a prospective, multicenter, non-interventional exploratory study designed to evaluate the relationship between immune fitness and clinical outcomes in patients aged 65 years or older with RRMM treated with standard-of-care chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies. Peripheral blood samples collected before treatment initiation will be analyzed to characterize T-cell differentiation, activation, senescence, exhaustion, and T-helper cell subsets using multiparametric immunophenotyping. Serum biomarkers, including soluble B-cell maturation antigen (sBCMA) and senescence-associated soluble markers, will also be assessed.
- The primary objective is to determine whether baseline immune profiles are associated with quality of response at 3 months after treatment initiation.
- Secondary objectives include evaluating the association between immune profiles and treatment-related toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), other neurological toxicities, and infectious complications. Exploratory analyses will integrate immune, geriatric, sarcopenia, and clinical variables using statistical approaches to identify novel predictors of efficacy, survival, and toxicity.
By combining immune phenotyping with frailty assessment, the PRIME study aims to improve biological risk stratification and support the development of more personalized treatment strategies for older patients with multiple myeloma.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 65 years old
- •Relapsed/refractory multiple myeloma
- •Eligible for a CAR-T cell or bispecific antibody therapies
排除标准
- •<65 years old
- •Active cancer other than myeloma
- •Active AL amyloidosis
- •Central nervous system (CNS) involvement
研究组 & 干预措施
Overall
Immunophenotyping arm
干预措施: immunophenotyping of lymphocyte (Other)
结局指标
主要结局
Rate of ≥VGPR or better according to IMWG criteria at 3 months.
时间窗: 3 months after the treatment
The association of VGPR and immune profile will be assessed.
次要结局
未报告次要终点