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Cited by 70Multiple Myeloma Research and TreatmentsCancer Immunotherapy and BiomarkersLymphoma Diagnosis and Treatment

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

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Sklavenitis-Pistofidis, Romanos, Aranha, Michelle P., Redd, Robert A., Baginska, Joanna, Haradhvala, Nicholas J., Hallisey, Margaret, Dutta, Ankit K., Savell, Alexandra +31 more·2022·Cancer Cell
DOI 10.1016/j.ccell.2022.10.017PMC PMC10019228
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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.

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  • All randomized studies (excluding active MM) show a clear advantage in progression-free survival, delaying MM progression, and preventing symptoms/organ damage; a recent study shows an overall survival advantage of early treatment.

    “Excluding patients with an active MM according to the most recent guidelines,3 all randomized studies have shown a clear advantage in progression-free survival, in delaying MM progression, in preventing symptoms/organ damage,107-109 and a recent study has also demonstrated the overall survival (OS) advantage of early treatment,111”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [108]

    The Introduction (page unavailable) reports that two phase III trials prolonged progression-free survival in high-risk smoldering myeloma and that one also prolonged overall survival. It does not establish the claim about all randomized studies or explicitly report prevention of symptoms or organ damage. The paper’s own phase II trial had no observation arm, so its Results and Discussion cannot demonstrate a comparative survival advantage. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Several trials have reported the advantages and risks of early intervention in high-risk SMM.

    “Several trials have reported the advantages and risks of early intervention in high risk SMM.105-112”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [108]

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Research works printed but not linked: 40

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Authors
Sklavenitis-Pistofidis, R., Aranha, M. P., Redd, R. A., Baginska, J., Haradhvala, N. J., Hallisey, M., Dutta, A. K., Savell, A., Varmeh, S., Heilpern-Mallory, D., Ujwary, S., Zavidij, O., Aguet, F., Su, N. K., Lightbody, E. D., Bustoros, M., Tahri, S., Mouhieddine, T. H., Wu, T., Flechon, L., Anand, S., Rosenblatt, J. M., Zonder, J., Vredenburgh, J. J., Boruchov, A., Bhutani, M., Usmani, S. Z., Matous, J., Yee, A. J., Jakubowiak, A., Laubach, J., Manier, S., Nadeem, O., Richardson, P., Badros, A. Z., Mateos, M.-V., Trippa, L., Getz, G., & Ghobrial, I. M.
Affiliations
  • Broad Institute (US)
  • Harvard University (US)
  • Dana-Farber Cancer Institute (US)
  • Beth Israel Deaconess Medical Center (US)
  • The Barbara Ann Karmanos Cancer Institute (US)
  • Saint Francis Hospital & Medical Center (US)
  • Levine Cancer Institute (US)
  • Colorado Blood Cancer Institute (US)
  • Massachusetts General Hospital (US)
  • University of Chicago (US)
  • Centre National de la Recherche Scientifique (FR)
  • University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (US)
Corresponding author
  • Getz, Gad
  • Ghobrial, Irene M.
ORCID
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2022-11
Volume
40
Issue
11
Pages
1358-1373.e8
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccell.2022.10.017
PMC
PMC10019228
OpenAlex
W4308952528
Cited by
70
References
7
Citations by year
2026: 21 · 2025: 18 · 2024: 21 · 2023: 8 · 2022: 2
FWCI
8.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Multiple Myeloma Research Foundation
  • International Myeloma Society
  • International Waldenstrom's Macroglobulinemia Foundation
  • Leukemia and Lymphoma Society (2316-17)
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • Minneapolis Medical Research Foundation
  • National Institutes of Health (R01 CA205954)
  • Stand Up To Cancer (SU2C-AACR-CT05-17)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords
smoldering multiple myeloma, high-risk smoldering myeloma, immunotherapy response biomarkers, elotuzumab, lenalidomide, dexamethasone, T cell receptor repertoire, immune cell composition, granzyme K, CD8+ effector memory T cells, prognostic factors, single-cell RNA sequencing
MeSH terms
Smoldering Multiple Myeloma, Lenalidomide, Humans, Immunologic Factors, Immunotherapy, Multiple Myeloma, Biomarkers, Clinical Trials, Phase II as Topic, Disease Progression

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