Association of PD-L1 Expression with Clinico-Pathological Factors and Treatment Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) from a Tertiary Care Cancer Center in Southern India
Authors: Modak Pradnya , Shivakumar Swarna , Priya Sabhari , Kumar Muthulingesh , Bhandarkar Varsha , Peddireddy Jahnavi , Premchandra Kalyani , Gokulanathan Narendhar , Nath Arya S. , Gawarle Neha Surendra , Mallarajapatna Govindarajan , P Anoop Nagraj , Patil Channappa Nagraj , Bhat Neema , Maurya Poonam , Sathyanarayanan Vishwanath 
Published: December 2024

Background: The prognostic significance of programmed death ligand 1 (PD-L1) levels in non-Hodgkin lymphoma (NHL) remains debatable, largely due to paucity of data, especially in the Indian subcontinent. This study explored association of PD-L1 expression with the clinical and pathological characteristics, treatment outcomes, and overall prognosis in diffuse large B-cell lymphoma (DLBCL).

Methodology: A prospective observational study was conducted (after IRB approval) on formalin-fixed paraffin-embedded (FFPE) tissue samples of 30 patients diagnosed with de novo DLBCL between April 2021 and April 2024. PD-L1 expression was evaluated using a modified Combined Positive Score (CPS) method (the percentage of positive lymphomatous and immune cells relative to the total tumor tissue cellularity). We performed immunohistochemistry using clone SP 22C3 to assess PD-L1 status. The study cohort included 30 DLBCL cases: 25 of DLBCL-NOS, 2 of primary mediastinal large B-cell lymphoma (PMBCL), and 2 of primary CNS lymphoma with DLBCL histology. For analysis, PDL1 levels were taken as &lt; 1% and ≥ 1%, &lt; 5% and ≥ 5%. Clinicopathological characteristics along with treatment outcomes, were recorded and analyzed.

Results: In this study, median age was 65 years (36-83yr), 45% were males and 55% females. 80% were at advanced Ann Arbor stages III and IV, 67% had comorbidities (Diabetes, Hypertension or IHD), and 73% had high-intermediate (R-IPI=3) to high R- IPI (R-IPI=4 or 5) scores. 66% were of GCB histology and 30% of non-GCB and 4% unclassifiable by Hans. Additionally, 4 cases showed Richter's transformation from follicular lymphoma (13%), 4 were double expressors (13%), and 7 were triple expressors (23%). Treatment included R-CHOP (n=26), R-DA EPOCH (n=2), MTR (n=1), and R-MPV (n=1).

26.66% had PD-L1 &lt;1% while 73.33% had PD-L1 ≥1%; 33.33% had PD-L1 &lt;5%, while 66.67% had PD-L1 ≥5%. There was statistically significant association between PD-L1 levels (≥1% and ≥5%) and advanced age (p&lt;0.001 and p=0.004), males (p=0.005 and p=0.003), GCB type (p&lt;0.001 and p=0.001), advanced stage (p&lt;0.001 and p=0.001), higher R-IPI score (p&lt;0.001 and p=0.001), primary refractory disease (p&lt;0.001 and p=1), but not with higher relapse rates (p=0.25 and p=0.429) .

PD-L1 ≥1% was significantly associated with high Ki67 (≥70%), and PD-L1 ≥5% was associated with higher SUV max (≥10) (p&lt;0.001). No association was found between PD-L1 levels and double expressors (p=1.0 and p=1.0) or triple expressors (p=0.2 and p=0.2) and those with B- symptoms (p=1.0).

At a median follow-up of 10 months, for those with PD-L1 &lt;1% compared to ≥1%, median progression-free survival (PFS) was 16 months vs 8.50 months (p=0.295); median overall survival (OS) was 16.6 vs 12 months (p=0.260). There was a statistically significant difference in 1-year PFS, with 90% for PD-L1 &lt;1% versus 50% for PD-L1 ≥1% (p=0.001).

For patients with PD-L1 &lt;5% compared to ≥5%, median PFS was 11 months vs 7 months (p=0.295); median OS was 14 vs 11.6 months (p=0.459). There was a statistically significant difference in 1-year PFS, with 54% for PD-L1 &lt;5% versus 20% for PD-L1 ≥5% (p=0.008).

Conclusion: The study indicates that high PD-L1 expression in DLBCL is linked to more aggressive clinicopathological features and adverse outcomes compared to those with low PD-L1 expression. However, overall survival association was not statistically significant. PD-L1 expression levels may serve as an independent predictor of PFS and OS in DLBCL. Limitations include small number of patients, short follow up and inclusion of 2 patients of primary CNS lymphoma, that might have affected the analysis minimally. Further research is essential to standardize the cutoff value and scoring method.