Peripheral blood immune cell profiling and response to BCMA CAR-T cell therapy in relapsed refractory multiple myeloma

Sep 30, 2026

Largest study reporting associations between baseline peripheral blood immune cell profiles and clinical outcomes after BCMA CAR-T therapy in relapsed/refractory multiple myeloma. Flow cytometric immunophenotyping quantifies T-cell subsets, B cells, and natural killer cells, including CD4+/CD8+ ratios, using defined reference ranges. Institutional review and retrospective cohorts of 110 patients receiving BCMA CAR-T are analyzed for treatment response on days 30 and 90, cytokine release syndrome, neurotoxicity, and immune profile abnormalities. Immune features are evaluated as continuous and dichotomized predictors for day 90 response and MRD negativity.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages4

Reading Time10 min

AccessFree to download

Study overview

Immune cell profiling methods

Patient cohort and treatment characteristics

Safety and response assessment

Statistical analysis and endpoints

Blood Cancer [Journal](Journal www.nature.com/bcj)[ www.nature.com/bcj](Journal www.nature.com/bcj) CORRESPONDENCE OPEN Peripheral blood immune cell proﬁling and response to BCMA CAR-T cell therapy in relapsed refractory multiple myeloma © The Author(s) 2026 Blood Cancer Journal (2026)16:4; [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1038/s41408-025-01443-1](10.1038/s41408-025-01443-1) To the editor: Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM) [1, 2] . Although BCMA CAR-T cell therapy induces deep and durable responses in most patients with RRMM, disease progression ultimately occurs in most cases. Studies in B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma have demonstrated that distinct CAR-T cell subsets exhibit differential functions in antitumor efﬁcacy and toxicity proﬁles [3, 4] . Peripheral blood and bone marrow immune proﬁling of multiple myeloma (MM) patients treated with CAR-T cell therapy and bispeciﬁc T-cell engagers has revealed enrichment of CD4+ T cells and memory T-cell populations, along with elevated CD4+ /CD8+ ratios, in treatment responders compared to non-responders [5] . The association between pre-treatment circulating immune cell populations and therapeutic efﬁcacy of BCMA CAR-T-cell therapy in RRMM remains inadequately characterized. We report the results of the largest study to date examining the association between baseline peripheral blood immune cell proﬁles and clinical outcomes following BCMA CAR-T cell therapy in patients with RRMM. Flow cytometric immunophenotyping was performed to assess T cell subsets, B cells, and natural killer cells. The T cell helper/ suppressor panel evaluated the following lymphocyte populations with their respective normal reference ranges: CD3+ T lymphocytes (64–82%, 1171–2005 cells/μL), CD3+CD4+ helper /inducer T lymphocytes (39–57%, 720–1348 cells/μL), CD3+CD8+ suppressor/ cytotoxic T lymphocytes (17–31%, 318–710 cells/μL), CD19+ B lymphocytes (8–16%, 151–343 cells/μL), and CD56+ natural killer lymphocytes (7–21%, 145–453 cells/μL). The CD4+/CD8+ ratio was calculated with a normal range of 1.00–3.60. For this test, we use BD Multitest 6-color TBNK reagent with TruCount tubes (CD3Fitc/ CD16&56Pe/CD45PerCP-Cy5.5/CD4 Pe-Cy7/CD19APC/CD8APC-Cy-7). Both relative percentages and absolute counts were determined for each cell population. CD3 represents the pan-T cell marker identifying all mature T lymphocytes, while CD4 and CD8 distinguish helper and cytotoxic T cell subsets, respectively. CD19 serves as a pan-B cell marker, and CD56 identiﬁes natural killer cells. Institutional Review Board approval was obtained from the University of Arkansas for Medical Sciences (UAMS) prior to study initiation. The study was performed in accordance with all applicable guidelines and regulations. Patient informed consent was waived given the retrospective nature of the investigation. A total of 110 patients with RRMM who received BCMA CAR-T therapy at the UAMS were included. The median age at diagnosis and at apheresis was 56.4 and 65.5 years, respectively. Extramedullary disease (EMD) was present in 17 (16%) of patients prior to CAR-T infusion. One-third of patients had high-risk disease at diagnosis as deﬁned by the second revision of the International Staging System for Multiple Myeloma (R2-ISS) (Table 1) . The median number of prior myeloma therapies was 6.5 (range, 1 to 15) . Most patients (94%) received at least one autologous stem cell transplantation (ASCT) . The majority of patients (74%) had penta-refractory disease, deﬁned as resistance to at least two agents in the immunomodulatory (IMiD) class, two in the proteosome-inhibitor (PI) class and an antiCD38 monoclonal antibody. Six patients received prior GPRC5Dbispeciﬁc antibody and 39% received prior anti-BCMA therapy (Supplementary Table 1) . The majority of patients required a single at

FAQs

What is the document’s primary focus regarding BCMA CAR-T therapy?

It evaluates how baseline peripheral blood immune cell profiles relate to clinical outcomes after BCMA CAR-T therapy in relapsed/refractory multiple myeloma.

How were immune cell subsets measured?

Flow cytometric immunophenotyping assessed T-cell subsets, B cells, and natural killer cells, with helper and cytotoxic populations defined by CD4 and CD8 markers and reference ranges provided.

Which outcomes were used as primary endpoints?

Primary endpoints included response on day 90 and day 90 measurable residual disease (MRD) negativity.

Sep 30, 2026

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