Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: Results from PETAL consortium.

Variances in global access to drugs and treatment practices make it challenging to understand the benefit of contemporary therapies in patients with relapsed and refractory (R/R) mature T-cell and NK-cell lymphomas (MTCL and MNKCL). We conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL. In PTCL-NOS and ALK- ALCL, patients with relapsed lymphoma demonstrated a superior median overall survival (OS) relative to refractory from the time of second-line treatment. We identified several independent predictors of OS for R/R lymphoma including age >60, primary refractory disease, histological subtype other than AITL, extranodal sites >1, Ki67 ≥40%, and absolute lymphocyte count <LLN. A multivariable model incorporating these formed the basis for a prognostic index for R/R TCL (PIRT), in which patients are stratified into low-risk (0-1 risk factor), intermediate-risk (2-3 risk factors), or high-risk (≥4 risk factors) groups, which were associated with 3-year OS of 57.14% (95% CI: 17.1-83.7), 23.3% (8.7-41.9), and 7% (0.4-26.9), respectively. Patients received either a "novel" single agent (SA, 35%) or cytotoxic chemotherapy (CC, 60%) for their second line treatment. Higher progression-free survival was observed with SA over CC for the entire cohort with a higher 3-year OS in AITL and ALK- ALCL. Among the SA, small molecule inhibitors demonstrated OS advantage relative to CC in AITL. Our results underscore efficacy of novel drugs and the potential of a new prediction model in informing heterogeneous prognosis within the R/R population of MTCL and MNKCL.

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