Prognostic value of interim PET in patients with extranodal natural killer/T-cell lymphoma treated with non-anthracycline containing l-asparaginase based regimen

Abstract

Abstract Background Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma predominantly involving the nasal cavity and nasopharynx. Despite advances with L-asparaginase-based regimens, rapid disease progression remains common, underscoring the need for enhanced risk stratification. While baseline Prognostic Index for Natural Killer cell lymphoma (PINK) and PINK with Epstein-Barr virus DNA (PINK-E) scoring provide initial risk assessment, it lacks dynamic evaluation during treatment. Therefore, we evaluated the prognostic value of interim positron emission tomography (PET) and its integration with the PINK-E scoring system to enable longitudinal risk assessment and improve prognostic accuracy. Methods We retrospectively analyzed 48 patients with ENKTL treated with L-asparaginase-based regimens and underwent interim PET analysis between May 2009 and May 2020. Patients with progressive disease on interim PET were excluded. PET images were evaluated using the Deauville score (DS) and the percentage decrease in maximum standardized uptake value (%ΔSUVmax). Patients were categorized by interim DS (iDS1-3 vs iDS4-5) and by %∆SUVmax (>61% vs ≤61%) using the first quartile cut-off (Q1=61%). The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS). Results A total of 48 patients were included (median age, 54 years; 60.4% male) with a median follow-up of 50.9 months. Four patients were excluded from %ΔSUVmax analysis due to missing baseline PET data. In multivariable analysis, %ΔSUVmax≤Q1 (n=11, 25.0%) independently predicted poor outcomes for both OS (adjusted HR, 6.32; p<0.001) and PFS (adjusted HR, 5.51; p<0.001), while iDS 4–5 (n=24, 50.0%) showed a trend toward significance for OS (adjusted HR, 2.20; p=0.076) but not for PFS. Among patients with iDS 4–5, %ΔSUVmax>Q1 (n=11) was associated with longer OS (median, 54.87 vs. 5.19 months; p=0.100) and PFS (median, 63.12 vs. 2.89 months; p=0.061) compared to ≤Q1 (n=11), though not statistically significant. Combining PINK-E and %ΔSUVmax stratified patients into three prognostic groups: low-risk (PINK-E low/intermediate + %ΔSUVmax>Q1, n=10), intermediate-risk (PINK-E low/intermediate + %ΔSUVmax≤Q1 or PINK-E high + %ΔSUVmax>Q1, n=27), and high-risk (PINK-E high + %ΔSUVmax≤Q1, n=7). Pairwise comparisons revealed significant differences in OS: low vs. intermediate (p=0.039), low vs. high ( p<0.001), and intermediate vs. high (p=0.002). For PFS, differences were significant between low vs. high (p<0.001) and intermediate vs. high (p<0.001), with a trend toward significance between low and intermediate groups (p=0.069). Conclusion Interim PET response measured by %ΔSUVmax offered significant prognostic value in ENKTL patients treated with L-asparaginase-based therapy. Integrating interim PET results with the PINK-E score enhanced risk stratification, enabling identification of high-risk patients who may benefit from intensified or alternative strategies.