Immune Fitness in Older Patients With Relapsed and Refractory Multiple Myeloma

NCT07674498 | Recruiting

• 1 other identifier: HUB20260367
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Myeloma Multiple

Keywords

multiple myeloma; immunosenescence; Exhaustion; T-fitness; T lymphocyte; elderly; T cell therapies

Outcome Measures

Primary Outcomes (1)

• Rate of ≥VGPR or better according to IMWG criteria at 3 months.

  The association of VGPR and immune profile will be assessed.

  3 months after the treatment

Study Arms (1)

Overall

OTHER

Immunophenotyping arm

Other: immunophenotyping of lymphocyte

Interventions

immunophenotyping of lymphocyte OTHER

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.

Overall

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Jules Bordet Institute: lead

Study Sites (3)

Institut Jules Bordet

Anderlecht, Brussels Capital, 1070, Belgium

RECRUITING

CHU Saint-Pierre

Brussels, Brussels Capital, 1000, Belgium

NOT YET RECRUITING

institut roi albert II

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

NOT YET RECRUITING

Related Publications (14)

• Ullrich F, Brockelmann PJ, Turki AT, Khan AM, Chiru ED, Vetter M, Tresckow BV, Wirth R, Cordoba R, Ortiz-Maldonado V, Fulop T, Neuendorff NR. Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma. J Immunother Cancer. 2024 Dec 2;12(12):e009462. doi: 10.1136/jitc-2024-009462.

  PMID: 39622581 BACKGROUND

• Cortes-Selva D, Perova T, Skerget S, Vishwamitra D, Stein S, Boominathan R, Lau O, Calara-Nielsen K, Davis C, Patel J, Banerjee A, Stephenson T, Uhlar C, Kobos R, Goldberg J, Pei L, Trancucci D, Girgis S, Wang Lin SX, Wu LS, Moreau P, Usmani SZ, Bahlis NJ, van de Donk NWCJ, Verona RI. Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in the MajesTEC-1 study. Blood. 2024 Aug 8;144(6):615-628. doi: 10.1182/blood.2023022823.

  PMID: 38657201 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Philipp N, Kazerani M, Nicholls A, Vick B, Wulf J, Straub T, Scheurer M, Muth A, Hanel G, Nixdorf D, Sponheimer M, Ohlmeyer M, Lacher SM, Brauchle B, Marcinek A, Rohrbacher L, Leutbecher A, Rejeski K, Weigert O, von Bergwelt-Baildon M, Theurich S, Kischel R, Jeremias I, Bucklein V, Subklewe M. T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals. Blood. 2022 Sep 8;140(10):1104-1118. doi: 10.1182/blood.2022015956.

  PMID: 35878001 BACKGROUND

• Bruins WSC, Smits F, Duetz C, Nasserinejad K, Groen K, Korst CLBM, de Jonge AV, Rentenaar R, Hageman T, Cosovic M, Eken M, Twickler I, Homan-Weert PM, Verkleij CPM, Frerichs K, Levin MD, van der Spek E, Nijhof IS, van Kampen R, van de Donk NWCJ, Zweegman S, Mutis T. Immune signatures in older patients with newly diagnosed multiple myeloma are associated with survival outcomes of first-line therapy irrespective of frailty levels. Hemasphere. 2025 Oct 5;9(10):e70210. doi: 10.1002/hem3.70210. eCollection 2025 Oct.

  PMID: 41054769 BACKGROUND

• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169.

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• Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27.

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• Lin Y, Qiu L, Usmani S, Joo CW, Costa L, Derman B, Du J, Einsele H, Fernandez de Larrea C, Hajek R, Ho PJ, Kastritis E, Martinez-Lopez J, Mateos MV, Mikhael J, Moreau P, Nagarajan C, Nooka A, O'Dwyer M, Schjesvold F, Sidana S, van de Donk NW, Weisel K, Zweegman S, Raje N, Otero PR, Anderson LD Jr, Kumar S, Martin T; International Myeloma Working Group. Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee. Lancet Oncol. 2024 Aug;25(8):e374-e387. doi: 10.1016/S1470-2045(24)00094-9. Epub 2024 May 28.

  PMID: 38821074 BACKGROUND

• Dimopoulos MA, Terpos E, Boccadoro M, Moreau P, Mateos MV, Zweegman S, Cook G, Engelhardt M, Delforge M, Hajek R, Schjesvold F, Gay F, Manier S, Weisel KC, Kaiser M, van de Donk NWCJ, Zamagni E, Rodriguez-Otero P, Perrot A, Driessen C, Bila J, Laane E, Dytfeld D, Touzeau C, Beksac M, Raab MS, Cavo M, Mohty M, Spencer A, Ludwig H, Einsele H, San-Miguel J, Sonneveld P. EHA-EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma. Nat Rev Clin Oncol. 2025 Sep;22(9):680-700. doi: 10.1038/s41571-025-01041-x. Epub 2025 Jul 7.

  PMID: 40624367 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Marie Vercruyssen, MD

CONTACT

+32497840746; marie.vercruyssen@hubruxelles.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 29, 2026
• Study Start: June 3, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 29, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3)