Immune Fitness in Older Patients With Relapsed and Refractory Multiple Myeloma

Официальное название

Prediction of Response Related to IMmune Age T Cell Fitness in Elderly Patients With Relapsed and Refractory Multiple Myeloma

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое immunophenotyping of lymphocyte
  Multiparametric flow cytometry will be used to characterize peripheral T-cell compartment, including differentiation status, senescence-associated phenotypes and exhaustion markers, as well as Th1/Th17 and Treg. The following markers will be used : CD57, CD25, CD3, CD45RO, CD38, CD27, CD8, CD4, CD45, KLRG1, CD127, CD28, TIGIT, CCR4, LAG-3, CD3, CCR6, CD8, CD4, CD45, PD-1, CXCR3, TIM-3. A serum sample will be collected to measure sBCMA and senescence-associated soluble markers.

Первичные конечные точки

• Rate of ≥VGPR or better according to IMWG criteria at 3 months. [Срок оценки: 3 months after the treatment]

Критерии участия

Критерии включения

• ≥ 65 years old
• Relapsed/refractory multiple myeloma
• Eligible for a CAR-T cell or bispecific antibody therapies

Критерии исключения

• <65 years old
• Active cancer other than myeloma
• Active AL amyloidosis
• Central nervous system (CNS) involvement

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Бельгия · 3 центра

• Institut Jules Bordet — Anderlecht
• CHU Saint-Pierre — Brussels
• institut roi albert II — Woluwe-Saint-Lambert

Публикации

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• Bruins WSC, Smits F, Duetz C, Groen K, Korst CLBM, de Jonge AV, Verkleij CPM, Rentenaar R, Cosovic M, Eken M, Twickler I, Homan-Weert PM, Sonneveld P, Moreau P, Claesen J, van de Donk NWCJ, Zweegman S, Mutis T. A T-cell-based metric of immune age predicts outcomes in older patients with myeloma receiving daratumumab-based therapy. Blood. 2025 Nov 20;146(21):2517-2530. doi: 10.1182/blood.2025028587 PMID 40829164
• Prabhala RH, Pelluru D, Fulciniti M, Prabhala HK, Nanjappa P, Song W, Pai C, Amin S, Tai YT, Richardson PG, Ghobrial IM, Treon SP, Daley JF, Anderson KC, Kutok JL, Munshi NC. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood. 2010 Jul 1;115(26):5385-92. doi: 10.1182/blood-2009-10-246660. Epub 2010 Apr 15. PMID 20395418
• Mehta PH, Fiorenza S, Koldej RM, Jaworowski A, Ritchie DS, Quinn KM. T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy. Front Immunol. 2021 Nov 25;12:780442. doi: 10.3389/fimmu.2021.780442. eCollection 2021. PMID 34899742
• Liu Z, Liang Q, Ren Y, Guo C, Ge X, Wang L, Cheng Q, Luo P, Zhang Y, Han X. Immunosenescence: molecular mechanisms and diseases. Signal Transduct Target Ther. 2023 May 13;8(1):200. doi: 10.1038/s41392-023-01451-2. PMID 37179335
• Rodriguez IJ, Lalinde Ruiz N, Llano Leon M, Martinez Enriquez L, Montilla Velasquez MDP, Ortiz Aguirre JP, Rodriguez Bohorquez OM, Velandia Vargas EA, Hernandez ED, Parra Lopez CA. Immunosenescence Study of T Cells: A Systematic Review. Front Immunol. 2021 Jan 15;11:604591. doi: 10.3389/fimmu.2020.604591. eCollection 2020. PMID 33519813
• Cai L, Zuo L, Wang G, Li Q, Ma C, Wu J, Sun C, Hu Y. T Cells Dysfunction in Multiple Myeloma. Immunotargets Ther. 2025 Sep 11;14:997-1014. doi: 10.2147/ITT.S534784. eCollection 2025. PMID 40959595

Идентификаторы

NCT: NCT07674498 · HUB20260367

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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