P211 | NEUTROPHIL-TO-LYMPHOCYTES RATIOS CAN PREDICT OUTCOMES AND TREATMENT RESPONSE IN MYELOFIBROSIS PATIENTS: A SINGLE-CENTER RETROSPECTIVE STUDY

Background: Myelofibrosis (MF) is the most symptomatic form of MPN and carries the worst outcome. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are novel inflammatory markers that have been investigated in MPNs. However, limited data are available concerning their impact on hematological features and clinical response in MF pts treated with JAK2 inhibitors (JAKi). Aim: To clarify the individual prognostic contribution of NLR, PLR, SII and SIRI, in a large cohort of MF patients (pts) including those treated with JAKi. Methods: The current study included 275 patients with MF (prefibrotic MF, overt MF and secondary MF), recruited from the CRIMM MPN database, based on availability of information on blood count, ANC, ALC and AMC at diagnosis (dg). In 144 additional pts these information were available at the onset of JAKi therapy. Results: At dg, median value of NLR was 3.6 (0.4 – 23.5), PLR 296.84 (3.2 – 1917.6), SII 1740 (5.8 – 20184.3), SIRI 1.67 (0.02 - 74.1). NLR and PLR at dg were associated with shorter OS, specific cut-off were identified as NLR >3.5 and PLR <178 (Figure 1A, B); furthermore, PLR<178 at dg was also associated to reduced 5y-LFS (74% vs 98% HR 9.4 IC95% 3.4-25.9, p<0.001). PLR<178 (17.6% vs 4.5%, p<0.001), lower SII (median 655 vs 1809 p<0.001) and higher SIRI (median 0.8 vs 1.8 p 0.024) were associated with an increased transfusion dependency (TD) at dg, as well as in pts initially transfusion-independent (TI). NLR >3.5 and PLR <178 overall predicted a more advanced disease (Bone marrow fibrosis <u>></u>2, presence of constitutional symptoms, JAK2 homozygous mutation). In 144 pts treated with JAKi, a reduction of at least 50% in NLR from baseline (BL) at week 12 (W12), correlated with spleen response (SR, according to 2013 IWG-MRT criteria) (p=0.003) and with shorter time to SR (Figure 1C). In pts achieving SR, median NLR at BL was higher in pts experiencing loss of SR (median 9.0 vs 4.8 p 0.026). Conversely, median PLR was higher in pts experiencing worsening of anemia at W12 (median 176 vs 112 p 0.012, defined as occurrence of Hb <10 or need of transfusion). Conclusions: Our study suggests that NLR and PLR deserve a prognostic value in predicting outcomes and are associated with clinical and biological features of MF pts when evaluated both at dg and during JAKi treatment.