Session: 637. Myelodysplastic Syndromes—Clinical Studies: Poster III
Hematology Disease Topics & Pathways:
Diseases, Adult, Biological Processes, MDS, Study Population, Myeloid Malignancies, inflammation, molecular interactions
Patients and Methods: We included 36 ECD patients for which BRAF status was determined. Biopsy samples were re-read in all cases. The density of inflammatory cells (lymphocytes and plasma cells) other than histiocytes was evaluated as mild (+), moderate (++), or marked (+++). Immunostaining was performed to detect PD-L1 (QR1Clone) in histiocytes and PD-1 (NAT105 clone) in lymphocytes. PD-L1 was assessed as percentage of positive histiocytes. The positivity of PD-L1 was defined as ≥ 5%. PD-1 immunostaining was evaluated as mild (+), moderate (++), or marked (+++).
Results: Overall, BRAFV600E was present in 19 patients (52.8%), MAP2K1 in 2 (5.5%) and NRAS in 1 (2.8 %). PD-L1 was positive in 15 patients (41.7%), PD-1 in 23 (63.8%) and both were found in 13 (36.1%). The intensity of inflammation in 21 patients (58.3%) was mild, moderate in 9 (25%) and high in 6 (16.7%). Among the 23 PD-1 positive cases, 15 (65.2%) were mild and 8 (34.8%) moderate. We found a strong association between PD-L1 positivity and intensity of inflammation: 13 PD-L1 positive patients were moderate/marked, vs 2 PD-L1 positive being mild; only 2 PD-L1 negative patients were moderate/marked, vs 19 PD-L1 negative being mild (p<0.001). The same association was seen between PD1 positivity and level of inflammation: 14 PD-1 positive patients had moderate/marked inflammation, vs 9 PD-1 positive patients with mild inflammation; 1 PD-1 negative patient had moderate/marked inflammation, vs 12 PD-1 negative with mild inflammation (p<0.01). We found a negative association between PD-L1 positivity and BRAFV600E mutation: 4 PD-L1 + patients were mutated vs 11 PD-L1 + being BRAFV600E Wild Type (WT); 15 PD-L1 - patients were mutated vs 6 PD-L1- being WT (p<0.01). No association was found between PD-1 postivity and BRAFV600E mutation. 80 % of patients which were PD-L1 - PD-1 + were BRAFV600E mutated. In the contrary, all patients PD-L1 + PD-1 - were WT.
Conclusions: We found a negative association between PD-L1 positivity and BRAFV600E mutation. Eleven patients only (30.5%) of ECD patients were PD-L1 and PD-1 negative. The recent success of immune checkpoint blockade therapy in some cancer types combined with the expression of immune checkpoint antigens in ECD samples suggests that such therapies should be investigated for refractory ECD.
Disclosures: No relevant conflicts of interest to declare.
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