To evaluate number of extranodal (EN) sites in nodal PTCL lymphomas (PTCL-NOS, TFH and ALCL ALK+/ALK-) and its specific location as a surrogate for overall survival (OS) and progression free survival (PFS). Also generate hypothesis for further molecular analysis.

T-cell Brazil project is a national, ambispective study of patients (pts) with histological diagnosis of PTCL diagnosed from January 2015 to December 2022. Approval for the study was obtained at the coordinating center (Samaritano Hospital – São Paulo) and at each participating center. Inclusion criteria was previously untreated patients age ≥ 19 years, with de novo PTCL lymphoma. Clinical information, initial therapy and response, subsequent therapies, along with survival status and cause of death were collected. Treatment outcome was determined by OS and PFS. REDcap Platform (by Vanderbilt) has been used to collect and store data and for analysis the IBM-SPSS v. 24 was applied. Kaplan-Meier method estimated the OS and PFS, whereas Log-Rank tests to compare its curves. This trial is registered at Clinical trials (NCT03207789).

Of 621 registered we selected 198 patients (pts) diagnosed with nodal PTCL with at least one EN involvement. Considering all 198 pts, there was a slight male predominance (63%); median age 53 years; 79% were staged III or IV; 81.5 were IPI 2 or more. Most frequently histology was PTCL-NOS (46%), followed by ALCL ALK+ (32%), ALCL ALK- (12.5%) and TFH (9.5%). The majority had B Symptoms (63%); 37.5% had Bone Marrow infiltration. The chemotherapy most frequently chosen were CHOEP (54.5%) followed by CHOP (19.5%); Transplant as consolidation was in 20% of the cases. Almost half of pts achieved complete response after first line (44%), although 38% relapsed. Cohort 1 (E N = 1) and 2 (EN 32) were similar regarding clinical characteristics, except, for stage III-IV (73% vs 96%; p <.0001); IPI 33 (37.5% vs. 82%; p <.0001) and ECOG (22 vs. 48%; p = .001), respectively. Therefore, translating in a more advanced disease in Cohort 2. The most common extranodal location in Cohort 1 was Skin/ Subcutaneous (35%), followed by gastrointestinal tract (18%) and lung (16%). NHL-T subtypes behaved similarly in this EN exploratory analysis, with a better OS and PFS in ALCL ALK+, followed by ALK- and PTCL-NOS. There was no difference in PFS in Cohort 1 and 2, but there was a slight difference in OS (55% vs. 42% in 12 months; p = 0.06), suggesting EN sites involvement assessed by CT and PET-CT as possible surrogate for outcomes in this population.

PTCL lymphomas account for 10-15% of all NHL. They are a heterogeneous group of infrequent neoplasms with a variable clinical course but prevalently aggressive behavior and high mortality rates. Despite IPI (International Prognostic Index) that include EN site in its variables, lack is known regarding EN location or impact on prognosis.

NHL-T is still unmet medical need considering suboptimal outcome in treatment and survival. New biological and clinical finding are still necessary to adequate stratify this group of pts, considering poor performance of IPI and PIT scores. Number and location of EN sites involvement may be a possible surrogate for outcome, which can be a reflect of a distinct biology, that needs further investigation. Registries are of importance considering rarity and poor prognosis of this diseases and an adequate instrument to hypothesis generation.