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. 2024 Apr 12;14(1):62.
doi: 10.1038/s41408-024-01051-5.

CD56 expression predicts response to Daratumumab-based regimens

Allen J Robinette  1 , Laila Huric  1 , Kameron Dona  1 , Don Benson  1 , Francesca Cottini  2
Affiliations

CD56 expression predicts response to Daratumumab-based regimens

Allen J Robinette et al. Blood Cancer J. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. CD56 expression predicts response to daratumumab therapy.
A Surface expression of CD56 in OPM-2 and H929 cells treated with DMSO or Dara 1 μg/mL for 48 h. Mean fluorescence intensity (MFI) value ratios are obtained normalizing to DMSO controls. n = 3 replicates. OPM-2 p = 0.041 (*); H929 p = 0.0358 (*). B Intracellular staining of CD56 in OPM-2 and H929 cells treated with DMSO or Dara 1 μg/mL for 1 h. MFI value ratios are obtained normalizing to DMSO controls. n = 3 replicates. OPM-2 p = 0.0145 (*); H929 p = 0.0217 (*). C Western blot analysis for CD56, MCL1, BCL2, and GAPDH in OPM-2 cells treated with DMSO and Dara 1 μg/mL for 48 h. D Quantitative PCR analysis for MCL1 (p = 0.05, *), BCL2 (p = 0.02, *), and CD56 (p = 0.12, ns) in OPM-2 cells treated with DMSO and Dara 1 μg/mL for 48 h (n = 2, 3 replicates). E Best responses to Dara therapy in 48 patients with <10% of CD56-expressing MM clonal cells (“Low CD56” group) or 104 patients with >10% of CD56-expressing MM clonal cells (“High CD56” group). In blue are reported the percentages of complete responses/very good partial responses (CR/VGPR), while in orange are the percentages of partial responses/minimal responses (PR/MR). p = 0.012. Percentages are included in the graph. F Progression-free survival (PFS) from the first day of Dara therapy in patients with less (n = 48, Low CD56-blue) or more than 10% of CD56-expressing MM clonal cells (n = 104, High CD56-fuchsia). Median PFS and 95% confidence intervals (CI) are reported in the insert of the plot. Log-rank p = 0.04. G PFS from the first day of Dara-IMiD therapy in patients with less (n = 24, Low CD56-blue) or more than 10% of CD56-expressing MM clonal cells (n = 60, High CD56-fuchsia). Immunomodulatory drugs (IMiDs) include lenalidomide or pomalidomide. Median PFS and 95% CI are reported in the insert of the plot. Log-rank p = 0.06.
Fig. 2
Fig. 2. CD56, CD38, and 1q+ status regulate responses to anti-CD38 monoclonal antibodies.
A Progression-free survival (PFS) from the first day of Dara therapy in patients with Low CD38, Low CD56 (n = 30, blue), High CD38, Low CD56 (n = 18, black), Low CD38, High CD56 (n = 46, fuchsia), and High CD38, High CD56 (n = 58, orange) disease. Median PFS and 95% confidence interval (CI) are reported in Table S3. Log-rank p < 0.001. B Regression analysis to correlate clone sizes of CD38- and CD56-expressing MM cells in 152 patients from our MM registry. Flow data were obtained before starting Dara therapy. R = 0.14; p < 0.0001. C Fold-changes of CD38 Mean Fluorescence Intensity (MFI) and mRNA levels in U266 control cells (CNT) or U266 cells overexpressing CD56. Ratio is normalized to the control cells. n = 2, 4 replicates. MFI p = 0.0009 (***); mRNA p = 0.032 (*). D Volcano plot showing differences in the RNA expression of 88 genes included in the described immune signature [8]. In red are highlighted upregulated genes, while in blue downregulated genes. E Fold-changes of PDL1 and BTLA MFI values in U266 control cells (CNT) or U266 cells overexpressing CD56 treated with DMSO or Dara 1 μg/mL for 48 h. Each MFI is normalized to the MFI of U266 control cells treated with DMSO. n = 2 replicates. CD56 + DMSO versus CD56 + Dara: CD274 p = 0.0112 (*); BTLA p = 0.0462 (*). F Fold-changes of PDL1 and BTLA MFI values in OPM-2 cells treated with DMSO or Dara 1 μg/mL for 48 h. n = 2 replicates. CD274 p = 0.0007 (***); BTLA p = 0.044 (*). G Percentage of 4-h Dara-induced ADCC lysis against MM.1S control cells (CNT) or MM.1S overexpressing CD56. Peripheral blood mononuclear cells derived from 4 healthy donors were used as effector cells, at an effector-to-target ratio of 25:1. n = 2 replicates. p = 0.04 (*). H CD38 and CD56 log2 expression values in 131 patients with 1q+ (either gains or amplifications) or 196 patients with normal 1q copy number and no other chromosomal abnormalities. CD38 1q+ versus 1q+ neg: p = 0.518, ns; CD56 1q+ versus 1q+ neg: p < 0.0001 (****). Blue solid lines indicate median values. Dotted black lines indicate the 25th and 75th percentiles. I PFS from the first day of Dara therapy in patients with Low CD56, 1q+ neg (n = 33, blue), Low CD56, 1q+ (n = 15, dark green), High CD56, 1q+ neg (n = 69, purple), and High CD56, 1q+ (n = 35, orange) disease. Median PFS and 95% CI are reported in Table S6. Log-rank p < 0.001.
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References

    1. Van de Donk N, Richardson PG, Malavasi F. CD38 antibodies in multiple myeloma: back to the future. Blood. 2018;131:13–29. doi: 10.1182/blood-2017-06-740944. - DOI - PubMed
    1. Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016;128:959–70. doi: 10.1182/blood-2016-03-703439. - DOI - PubMed
    1. Chemlal D, Varlet E, Machura A, Ovejero S, Requirand G, Robert N, et al. EZH2 targeting induces CD38 upregulation and response to anti-CD38 immunotherapies in multiple myeloma. Leukemia. 2023;37:1925–8. doi: 10.1038/s41375-023-01983-0. - DOI - PMC - PubMed
    1. Fedele PL, Willis SN, Liao Y, Low MS, Rautela J, Segal DH, et al. IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of Ikaros and Aiolos. Blood. 2018;132:2166–78. doi: 10.1182/blood-2018-05-850727. - DOI - PubMed
    1. Robillard N, Wuilleme S, Moreau P, Bene MC. Immunophenotype of normal and myelomatous plasma-cell subsets. Front Immunol. 2014;5:137. doi: 10.3389/fimmu.2014.00137. - DOI - PMC - PubMed

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