达拉图穆马
多发性骨髓瘤
医学
肿瘤科
内科学
免疫系统
公制(单位)
免疫疗法
不确定意义的单克隆抗体病
免疫学
来那度胺
单克隆
抗体
单克隆抗体
运营管理
经济
作者
Wassilis S.C. Bruins,Febe Smits,Carolien Duetz,Kaz Groen,Charlotte L.B.M. Korst,A. Vera de Jonge,Christie P.M. Verkleij,Rosa Rentenaar,Meliha Cosovic,Merve Eken,Inoka Twickler,Paola M. Homan‐Weert,Pieter Sonneveld,Philippe Moreau,Jürgen Claesen,Niels W.C.J. van de Donk,Sonja Zweegman,Tuna Mutis
出处
期刊:Blood
[Elsevier BV]
日期:2025-08-19
卷期号:146 (21): 2517-2530
被引量:4
标识
DOI:10.1182/blood.2025028587
摘要
ABSTRACT: Immunotherapy has transformed the treatment landscape of multiple myeloma (MM), a hematological cancer predominantly affecting older individuals. Yet, whether immune aging, shaped by intrinsic aging processes, genetics, and external factors, affects treatment efficacy remains unclear. To address this, we investigated the influence of age on the immune system in patients with MM and explored whether immune aging associates with clinical outcomes in older patients. Using flow cytometry, we conducted high-dimensional profiling of T cells and natural killer cells in peripheral blood and bone marrow samples of 124 older (>65 years) and 145 younger (≤65 years) patients with newly diagnosed MM (ages 34-92 years) enrolled in the HOVON-143 and CASSIOPEIA/HOVON-131 trials. On average, older patients exhibited a more activated, differentiated, and senescent T-cell compartment than younger patients. Nonetheless, substantial interindividual variation in T-cell subset frequencies within both age groups indicated that calendar age inadequately reflects an individual's immune status. We therefore developed an immune clock on high-dimensional phenotypic T-cell data to quantify each patient's "immune age," revealing substantial variation in immune ages among patients of similar calendar age. Importantly, immune age appeared a stronger predictor of clinical outcomes than calendar age in older, nonfit patients with newly diagnosed MM receiving daratumumab-ixazomib-dexamethasone, even after adjusting for frailty and other established risk factors. Overall, these findings highlight immune age as a clinically relevant composite metric that better reflects a patient's immune status than their calendar age. Validating this methodology in other immunotherapy settings may improve our ability to predict immunotherapy efficacy in older patients with MM or other hematological cancers.
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