Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma.
Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma.
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DOI：
10.1016/j.ccell.2022.10.017
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发表时间：
2022-11-14
期刊：
影响因子：
50.3
通讯作者：
Ghobrial, Irene M.
中科院分区：
文献类型：
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作者：
Sklavenitis-Pistofidis, Romanos;Aranha, Michelle P.;Redd, Robert A.;Baginska, Joanna;Haradhvala, Nicholas J.;Hallisey, Margaret;Dutta, Ankit K.;Savell, Alexandra;Varmeh, Shohreh;Heilpern-Mallory, Daniel;Ujwary, Sylvia;Zavidij, Oksana;Aguet, Francois;Su, Nang K.;Lightbody, Elizabeth D.;Bustoros, Mark;Tahnri, Sabrin;Mouhieddine, Tarek H.;Wu, Ting;Flechon, Lea;Anand, Shankara;Rosenblatt, Jacalyn M.;Zonder, Jeffrey;Vredenburgh, James J.;Boruchov, Adam;Bhutani, Manisha;Usmani, Saad Z.;Matous, Jeffrey;Yee, Andrew J.;Jakubowiak, Andrzej;Laubach, Jacob;Manier, Salomon;Nadeem, Omar;Richardson, Paul;Badros, Ashraf Z.;Mateos, Maria-Victoria;Trippa, Lorenzo;Getz, Gad;Ghobrial, Irene M.
郁积性多发性骨髓瘤（SMM）患者的观察，直到进展，但早期治疗可能会改善结果。我们在高危SMM患者中进行了一项Elotuzumab、来那度胺和地塞米松（EloLenDex）的II期试验，并对来自患者和健康供体（HD）的149份骨髓（BM）和外周血（PB）样本进行了单细胞RNA和T细胞受体（TCR）测序。我们发现早期使用EloLenDex治疗是安全有效的，并提供了患者免疫细胞组成和TCR库多样性改变的全面表征。重要的是，我们发现患者的免疫细胞组成与HD的相似性可能在诊断和治疗后具有预后相关性，并且GZMK+ CD 8+效应记忆T细胞的丰度可能与治疗反应相关。最后，我们发现了在BM和PB中观察到的免疫改变之间的相似性，这表明基于PB的免疫分析可能具有诊断和预后效用。Sklavenitis-Pistofidis等人报告了EloLenDex在高风险郁积型多发性骨髓瘤患者中的II期试验结果，并使用单细胞RNA测序来鉴定结果的生物标志物。他们表明，免疫细胞组成影响无进展生存期，并且基于血液的免疫分析可以检测骨髓中观察到的免疫改变。
Patients with Smoldering Multiple Myeloma (SMM) are observed until progression, but early treatment may improve outcomes. We conducted a Phase II trial of Elotuzumab, Lenalidomide, and Dexamethasone (EloLenDex) in patients with high-risk SMM and performed single-cell RNA and T cell Receptor (TCR) sequencing on 149 bone marrow (BM) and peripheral blood (PB) samples from patients and healthy donors (HD). We find that early treatment with EloLenDex is safe and effective and provide a comprehensive characterization of alterations in immune cell composition and TCR repertoire diversity in patients. Importantly, we show that the similarity of a patient’s immune cell composition to that of HD may have prognostic relevance at diagnosis and post-treatment, and the abundance of GZMK+ CD8+ effector memory T cells may be associated with treatment response. Lastly, we uncover similarities between immune alterations observed in the BM and PB, suggesting that PB-based immune profiling may have diagnostic and prognostic utility. Sklavenitis-Pistofidis et al. report results of a Phase II trial of EloLenDex in patients with high-risk smoldering multiple myeloma and use single-cell RNA sequencing to identify biomarkers of outcome. They show that immune cell composition impacts progression-free survival and that blood-based immune profiling can detect immune alterations observed in the marrow.
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影响因子：
--
作者：
Hallisey M;Dennis J;Abrecht C;Pistofidis RS;Schork AN;Lightbody ED;Heilpern-Mallory D;Severgnini M;Ghobrial IM;Hodi FS;Baginska J
通讯作者：
Baginska J
影响因子：
30.5
作者：
Galletti G;De Simone G;Mazza EMC;Puccio S;Mezzanotte C;Bi TM;Davydov AN;Metsger M;Scamardella E;Alvisi G;De Paoli F;Zanon V;Scarpa A;Camisa B;Colombo FS;Anselmo A;Peano C;Polletti S;Mavilio D;Gattinoni L;Boi SK;Youngblood BA;Jones RE;Baird DM;Gostick E;Llewellyn-Lacey S;Ladell K;Price DA;Chudakov DM;Newell EW;Casucci M;Lugli E
通讯作者：
Lugli E
影响因子：
12.8
作者：
Mateos MV;Kumar S;Dimopoulos MA;González-Calle V;Kastritis E;Hajek R;De Larrea CF;Morgan GJ;Merlini G;Goldschmidt H;Geraldes C;Gozzetti A;Kyriakou C;Garderet L;Hansson M;Zamagni E;Fantl D;Leleu X;Kim BS;Esteves G;Ludwig H;Usmani S;Min CK;Qi M;Ukropec J;Weiss BM;Rajkumar SV;Durie BGM;San-Miguel J
通讯作者：
San-Miguel J
影响因子：
48
作者：
Korsunsky, Ilya;Millard, Nghia;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G