Prognostic Significance of the Dynamic Change of Programmed Death-ligand 1 Expression in Patients with Multiple Myeloma

Abstract

Background The inhibition of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway has been shown to be an effective targeted therapy in fighting both solid organ cancers and hematological malignancies. PD-L1 expression also serves as a prognostic marker in various cancers. However, the expression of PD-L1 and its prognostic significance in multiple myeloma remains largely unknown. Methods Immunohistochemistry staining of PD-L1 was performed in bone marrow biopsy samples (total of 85 samples) in 32 myeloma patients receiving autologous stem cell transplant (ASCT) at various time points: before ASCT, post-ASCT, and/or at relapse after ASCT. More than 1% of myeloma cells with PD-L1 staining was considered a positive expression of PD-L1. A correlation analysis was performed between post-ASCT overall survival (OS) and the status of PD-L1 expression. Results In this pilot study, a total of 11 patients (34%) out of our cohort (32 patients) were positive for PD-L1 expression at least once during the course of the disease. A dynamic change of PD-L1 expression was noted in three patients converting from negative (before ASCT) to positive (post-ASCT) and two patients converting from positive (before ASCT) to negative (post-ASCT). Patients with positive PD-L1 expression persisting or occurring post-ASCT had shorter post-ASCT overall survival than those with negative PD-L1 expression post-ASCT (median survival: 13 vs 23 months, p<0.05). No significant differences were detected in the known prognostic factors between these two groups at the time of ASCT. Pre-transplant PD-L1 expression status, however, showed no significant impact on post-ASCT overall survival. Furthermore, a few patients switching from positive PD-L1 expression before ASCT to negative PD-L1 expression post-ASCT had a relatively good post-ASCT overall survival (n=2, overall survival of 29 and 56 months, respectively). Conclusion Immunohistochemistry can be reliably used for measuring PD-L1 expression in decalcified marrow core biopsy materials. Our results suggest that positive PD-L1 expression persisting/occurring post-ASCT could be an adverse prognostic marker for post-ASCT OS. Additionally, PD-L1 expression appears to be dynamic and is subjected to change after ASCT. Our findings suggest that periodically monitoring PD-L1 expression in patients with multiple myeloma post-ASCT is warranted. Further studies are needed to confirm our initial observation and to evaluate if timely intervention with PD-L1 blockade can improve post-ASCT outcomes in myeloma patients.