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Multicenter Study
. 2023 Dec 12;7(23):7331-7345.
doi: 10.1182/bloodadvances.2023011169.

High PDL1/PDL2 gene expression correlates with worse outcome in primary mediastinal large B-cell lymphoma

Vincent Camus  1   2 , Pierre-Julien Viailly  2 , Fanny Drieux  3 , Elena-Liana Veresezan  3 , Pierre Sesques  4 , Corinne Haioun  5 , Eric Durot  6 , Martine Patey  7 , Cédric Rossi  8 , Laurent Martin  9 , Vinciane Rainville  2 , Elodie Bohers  2 , Philippe Ruminy  2 , Dominique Penther  2   10 , Sophie Kaltenbach  11 , Julie Bruneau  12   13 , Jérome Paillassa  14 , Olivier Tournilhac  15 , Alexandre Willaume  16 , Chloé Antier  17 , Julien Lazarovici  18 , Emilie Lévêque  19 , Pierre Decazes  20 , Stéphanie Becker  20 , David Tonnelet  20 , Alina Berriolo-Riedinger  21 , Philippe Gaulard  22 , Hervé Tilly  1   2 , Thierry Jo Molina  13 , Alexandra Traverse-Glehen  23 , Fabrice Jardin  1   2
Affiliations
Multicenter Study

High PDL1/PDL2 gene expression correlates with worse outcome in primary mediastinal large B-cell lymphoma

Vincent Camus et al. Blood Adv. .

Abstract

Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive B-cell lymphoma with an unusually good prognosis, except for 10-15% of chemotherapy-refractory cases. To identify earlier these higher risk patients, we performed molecular characterization of a retrospective multicenter cohort of patients treated with firstline immunochemotherapy. The traits of the patients with gene-expression profiling data (n = 120) were as follows: median age of 34 years (range, 18-67 years); female sex, 58.3%; elevated lactate dehydrogenase, 82.5%; Eastern Cooperative Oncology Group performance status score of 0 to 1, 85.7%; Ann Arbor stage I/II, 55%; International Prognostic Index score of 1 to 2, 64.4%; and median metabolic tumor volume, 290.4 cm3 (range, 15.7-1147.5 cm3). Among all 137 markers tested for correlation with survival data, only programmed death-ligand (PDL) 1 and PDL2 expression showed a prognostic impact. Overall, both PDL1 and PDL2 genes were highly expressed in 37 patients (30.8%; PDL1high/PDL2high). The baseline clinical characteristics of patients with PDL1high/PDL2high were similar to those of other patients. In univariate analysis, PDL1high/PDL2high status was associated with poor progression-free survival (PFS) (hazard ratio [HR], 4.292) and overall survival (OS; HR, 8.24). In multivariate analysis, PDL1high/PDL2high status was an independent prognostic factor of adverse outcomes (PFS: HR, 5.22; OS: HR, 10.368). We validated these results in an independent cohort of 40 patients and confirmed the significant association between PDL1high/PDL2high status and inferior PFS (HR, 6.11). High PDL1/PDL2 gene expression defines a population with strong immune privilege and poorer outcomes from standard chemotherapy who might benefit from firstline checkpoint inhibitor therapy.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Study overview. (A) Study flowchart. (B) Venn diagram representing the different subcohorts of the study (histology set: n = 194; NGS set: n = 128; and GEP set: n = 120).
Figure 2.
Figure 2.
Heat map representing the mutational landscape of the PMBL cohort. SNV, single nucleotide variant.
Figure 3.
Figure 3.
High gene expression of both PDL1 and PDL2 correlated with poorer outcome. (A) PFS and (B) OS according to PDL1/PDL2 gene expression status (assessed by RT-MLPSeq) in the GEP set from the PMBL LYSA cohort (n = 120). Within the GEP set (n = 120), we identified a subset of 37 of 120 patients (30.8%) with high gene expression of the PDL1 and PDL2 genes (PDL1high/PDL2high; cutoff: median expression of each gene: PDL1 = 0.402; PDL2 = 9.147).
Figure 4.
Figure 4.
B2M mutations correlated with poorer outcome. (A) PFS and (B) OS according to B2M mutation status in the NGS set from the PMBL LYSA cohort (n = 128).
Figure 5.
Figure 5.
Validation cohort for PDL1/PDL2 high gene expression prognostic impact. (A) PFS and (B) OS according to PDL1/PDL2 gene expression status (assessed by RT-MLPSeq) in the independent Centre Henri Becquerel validation cohort (n = 40).
See this image and copyright information in PMC

References

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