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Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma.

ABSTRACT: 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 (HDs). 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. We show that the similarity of a patient's immune cell composition to that of HDs may have prognostic relevance at diagnosis and after treatment and that the abundance of granzyme K (GZMK)+ CD8+ effector memory T (TEM) cells may be associated with treatment response. Last, we uncover similarities between immune alterations observed in the BM and PB, suggesting that PB-based immune profiling may have diagnostic and prognostic utility.

SUBMITTER: Sklavenitis-Pistofidis R 

PROVIDER: S-EPMC10019228 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma.

Sklavenitis-Pistofidis Romanos R   Aranha Michelle P MP   Redd Robert A RA   Baginska Joanna J   Haradhvala Nicholas J NJ   Hallisey Margaret M   Dutta Ankit K AK   Savell Alexandra A   Varmeh Shohreh S   Heilpern-Mallory Daniel D   Ujwary Sylvia S   Zavidij Oksana O   Aguet Francois F   Su Nang K NK   Lightbody Elizabeth D ED   Bustoros Mark M   Tahri Sabrin S   Mouhieddine Tarek H TH   Wu Ting T   Flechon Lea L   Anand Shankara S   Rosenblatt Jacalyn M JM   Zonder Jeffrey J   Vredenburgh James J JJ   Boruchov Adam A   Bhutani Manisha M   Usmani Saad Z SZ   Matous Jeffrey J   Yee Andrew J AJ   Jakubowiak Andrzej A   Laubach Jacob J   Manier Salomon S   Nadeem Omar O   Richardson Paul P   Badros Ashraf Z AZ   Mateos Maria-Victoria MV   Trippa Lorenzo L   Getz Gad G   Ghobrial Irene M IM  

Cancer cell 20221101 11

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 (HDs). We find that early treatment with EloLenDex is safe and effective and provide a comprehensive  ...[more]

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