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PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

ABSTRACT: PD-L1 expression is associated with poor prognosis, although this relationship is unclear in bone marrow-derived haematologic malignancies, including multiple myeloma. We aimed to determine whether PD-L1 expression could predict the prognosis of newly diagnosed multiple myeloma (NDMM). We evaluated 126 NDMM patients (83, retrospectively; 43, prospectively) who underwent bone marrow examinations. Bone marrow aspirates were analysed for PD-L1 expression, categorized as low or high expression, using quantitative immunofluorescence. High PD-L1 expression could independently predict poor overall survival (OS) (95% CI?=?1.692-8.346) in multivariate analysis. On subgroup analysis, high PD-L1 expression was associated with poor OS (95% CI?=?2.283-8.761) and progression-free survival (95% CI?=?1.024-3.484) in patients who did not undergo autologous stem cell transplantation (ASCT) compared with those who did. High PD-L1 expression was associated with poor OS despite frontline treatments with or without immunomodulators. Thus, PD-L1 expression can be a useful prognosis predictor in NDMM patients, whereas ASCT may be used in patients with high PD-L1 expression. We developed a prognostic nomogram and found that a combination of PD-L1 expression in bone marrow plasma cells and clinical parameters (age, cytogenetics, and lactate dehydrogenase) effectively predicted NDMM prognosis. We believe that our nomogram can help identify high-risk patients and select appropriate treatments.

SUBMITTER: Lee BH

PROVIDER: S-EPMC7387472 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

Lee Byung-Hyun BH Park Yong Y Kim Ji Hye JH Kang Ka-Won KW Lee Seung Jin SJ Kim Seok Jin SJ Kim Byung Soo BS

Scientific reports 20200728 1

PD-L1 expression is associated with poor prognosis, although this relationship is unclear in bone marrow-derived haematologic malignancies, including multiple myeloma. We aimed to determine whether PD-L1 expression could predict the prognosis of newly diagnosed multiple myeloma (NDMM). We evaluated 126 NDMM patients (83, retrospectively; 43, prospectively) who underwent bone marrow examinations. Bone marrow aspirates were analysed for PD-L1 expression, categorized as low or high expression, usin ...[more]

PMID: 32724129

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Project description:BackgroundThe PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1/PD-1 expression by MM cells and bone marrow (BM) microenvironment cells. The unmet need to identify patients which could benefit from this therapeutic approach prompts us to evaluate the BM expression profile of PD-L1/PD-1 axis across the different stages of the monoclonal gammopathies.MethodsThe PD-L1/PD-1 axis was evaluated by flow cytometry in the BM samples of a total cohort of 141 patients with monoclonal gammopathies including 24 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), 38 patients with smoldering MM (SMM), and 79 patients with active MM, including either newly diagnosed or relapsed-refractory patients. Then, data were correlated with the main immunological and clinical features of the patients.ResultsFirst, we did not find any significant difference between MM and SMM patients in terms of PD-L1/PD-1 expression, on both BM myeloid (CD14+) and lymphoid subsets. On the other hand, PD-L1 expression by CD138+ MM cells was higher in both SMM and MM as compared to MGUS patients. Second, the analysis on the total cohort of MM and SMM patients revealed that PD-L1 is expressed at higher level in CD14+CD16+ non-classical monocytes compared with classical CD14+CD16- cells, independently from the stage of disease. Moreover, PD-L1 expression on CD14+ cells was inversely correlated with BM serum levels of the anti-tumoral cytokine, IL-27. Interestingly, relapsed MM patients showed an inverted CD4+/CD8+ ratio along with high levels of pro-tumoral IL-6 and a positive correlation between %CD14+PD-L1+ and %CD8+PD-1+ cells as compared to both SMM and newly diagnosed MM patients suggesting a highly compromised immune-compartment with low amount of CD4+ effector cells.ConclusionsOur data indicate that SMM and active MM patients share a similar PD-L1/PD-1 BM immune profile, suggesting that SMM patients could be an interesting target for PD-L1/PD-1 inhibition therapy, in light of their less compromised and more responsive immune-compartment.

Project description:Classical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction through Janus kinase 2-signal transducers and activators of transcription signaling. The unique composition of cHL limits its analysis with high-throughput genomic assays. Therefore, the precise incidence, nature, and prognostic significance of PD-L1/PD-L2 alterations in cHL remain undefined.We used a fluorescent in situ hybridization assay to evaluate CD274/PD-L1 and PDCD1LG2/PD-L2 alterations in 108 biopsy specimens from patients with newly diagnosed cHL who were treated with the Stanford V regimen and had long-term follow-up. In each case, the frequency and magnitude of 9p24.1 alterations-polysomy, copy gain, and amplification-were determined, and the expression of PD-L1 and PD-L2 was evaluated by immunohistochemistry. We also assessed the association of 9p24.1 alterations with clinical parameters, which included stage (early stage I/II favorable risk, early stage unfavorable risk, advanced stage [AS] III/IV) and progression-free survival (PFS).Ninety-seven percent of all evaluated cHLs had concordant alterations of the PD-L1 and PD-L2 loci (polysomy, 5% [five of 108]; copy gain, 56% [61 of 108]; amplification, 36% [39 of 108]). There was an association between PD-L1 protein expression and relative genetic alterations in this series. PFS was significantly shorter for patients with 9p24.1 amplification, and the incidence of 9p24.1 amplification was increased in patients with AS cHL.PD-L1/PD-L2 alterations are a defining feature of cHL. Amplification of 9p24.1 is more common in patients with AS disease and associated with shorter PFS in this series. Further analyses of 9p24.1 alterations in patients treated with standard cHL induction regimens or checkpoint blockade are warranted.

Dataset Information

PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

Publications

PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

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