BCMA-Positive Vesicles in Myeloma Patients: Response and Side Effects | Oncotarget
Channel: Oncotarget
Date: 2023-12-04

Oncotarget #published this #trending research #paper on December 1, 2023 in Volume 14, entitled, “Plasma levels of BCMA-positive extracellular vesicles correlate to response and side effects in myeloma patients treated with belantamab-mafodotin" by researchers from the Department of Hematology and Oncology, Städtisches Klinikum Braunschweig, Braunschweig, Germany; Department of Hematology, Oncology and Palliative Care, Heidekreis-Klinikum, Walsrode, Germany.
#cancer #myeloma #eryptosis #drugdiscovery #plasma #research #researchpaper #cancerresearch #oncology #openaccess #openscience #peerreview #journal #publication #publishing #meded 

DOI - https://doi.org/10.18632/oncotarget.28538

Correspondence to - Arne Trummer - arne.trummer@heidekreis-klinikum.de

Abstract

In myeloma patients, high levels of soluble BCMA (sBCMA) can limit the efficacy of BCMA-directed therapies. Belantamab-mafodotin is a BCMA antibody-drug conjugate and shows good overall response rates in heavily pretreated patients but progression-free survival data are poor. As the drug induces apoptosis, we hypothesized that sBCMA includes extracellular vesicles (EV) and thus evaluated numbers of BCMA-EV before and during belantamab therapy in 10 myeloma patients. BCMA-EV were significantly higher in patients prior to Belantamab (median: 3227/μl; p = .013) than in other myeloma patients before therapy (n = 10; 1082/μl) or healthy volunteers (n = 10; 980/μl). During therapy, BCMA-EV showed a significant increase to a maximum of 8292/μl (p = .028). Maximal changes in BCMA-EV (Δmax = BCMA-EV at C1/maximal BCMA-EV) showed a strong inverse, logarithmic correlation (r = −.950; p less than .001) with FLC ratio changes (Δmax = FLC ratio at C1/minimal FLC ratio) and BCMA-EV peaks often preceded FLC progression. Correlating increase of LDH and BCMA-EV levels, together with clinical symptoms, point to a mafodotin-induced eryptosis. In summary, BCMA-EV are a part of sBCMA, peak levels precede progression, and their measurement might be helpful in identifying resistance mechanisms and side effects of BCMA targeted therapies.

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Keywords - cancer, myeloma, b cell maturation antigen, extracellular vesicles, belantamab-mafodotin, eryptosis

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