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November 13, 2019Blood

Multidimensional Single Cell Analysis Shows Increased T/NK Cell Subsets in Both Blood and Bone Marrow of Iberdomide (CC-220) Treated Relapsed/Refractory Multiple Myeloma Patients

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Authors

MAMichael AmatangeloOOOliver Van OekelenARAdeeb Rahman

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Overview

Clinical trial demonstrates Iberdomide expands and activates cytotoxic T and natural killer cells in relapsed multiple myeloma, indicating enhanced antitumor immune remodeling.

Key Points

  • To evaluate the pharmacodynamic immunomodulatory effects of iberdomide on peripheral blood and bone marrow immune cell subsets in patients with relapsed/refractory multiple myeloma.
  • Phase 1/2 clinical trial (NCT02773030) evaluating iberdomide (0.3–1.3 mg QD, Days 1–21 of 28-day cycles) as monotherapy or with dexamethasone in 95 relapsed/refractory multiple myeloma patients.
  • Peripheral blood was profiled longitudinally by flow cytometry (n=90; Cycle 1 Day 1 vs. Cycle 2 Day 15) to track proliferation (Ki67), activation (HLA-DR), and differentiation markers.
  • Bone marrow aspirates (screening n=10, Cycle 2 Day 15 n=6) were evaluated for immune microenvironment remodeling using mass cytometry (CyTOF) and single-cell RNA sequencing.
  • Peripheral blood immune profiling showed median increases in total NK cells (35.5%) and proliferating NK cells (74.2%), alongside dose-dependent proliferation increases in CD4+ (92.3%) and CD8+ (116.0%) T cells.
  • Bone marrow mass cytometry showed total NK cells increased from 6.05% to 9.91% and CD16+ cytolytic NK cells rose from 35.9% to 42.4%, while effector memory CD8+ T cells increased from 26.7% to 39.5% and naive CD8+ T cells declined from 6.42% to 2.14%.
  • Single-cell transcriptomics revealed elevated expression of cytolytic genes (NKG7, GZMB) and interferon response genes (IFNG, TNF) in bone marrow CD8+ T cells, accompanied by an increase in CD4+ regulatory T cells from 0.72% to 5.06%.

Cite This Study

Amatangelo et al. (2019) studied this question.

synapsesocial.com/papers/6a0f82612badbc352afe44d8https://doi.org/10.1182/blood-2019-126146
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Iberdomide (IBER) in Combination with Dexamethasone (DEX) in Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Anti-B-Cell Maturation Antigen (BCMA)-Exposed Cohort of the CC-220-MM-001 Trial2022 · 11 citations
  2. 2Longitudinal analysis of MRD negativity and immune dynamics in patients with transplant-ineligible newly diagnosed multiple myeloma treated with iberdomide, daratumumab, and dexamethasone from the CC-220-MM-001 trial2025
  3. 3Pharmacodynamic changes in tumor and immune cells drive iberdomide’s clinical mechanisms of activity in relapsed and refractory multiple myeloma2024 · 5 citations
  4. 4Iberdomide plus daratumumab and dexamethasone (IberDd) in patients with newly diagnosed multiple myeloma by renal function: A subgroup analysis of the CC-220-MM-001 trial2025
  5. 5Iberdomide increases innate and adaptive immune cell subsets in the bone marrow of patients with relapsed/refractory multiple myeloma2024 · 19 citations