Global outcomes and prognosis for relapsed/refractory mature T-cell and NK-cell lymphomas: results from the PETAL consortium
Jessy Xinyi Han, Min Jung Koh, Leora Boussi, Mark N Sorial, Sean M. McCabe, Luke Peng, Shambhavi Singh, Ijeoma Julie Eche, Judith Gabler, María José Fernández, Caroline T. MacVicar, Aditya Ramesh Garg, A. DiSciullo, Kusha Chopra, Alexandra W Lenart, Emmanuel Nwodo, Jeffrey A. Barnes, Min Ji Koh, Eliana Miranda, Carlos Chiattone, Robert Stuver, Sarah McCue Horwitz, Mwanasha H. Merrill, Eric D. Jacobsen, Martina Manni, Monica Civallero, Tetiana Skrypets, Athina Lymboussaki, Massimo Federico, Yu Ri Kim, Jin Seok Kim, Y. Choi, Thomas Eipe, Tanuja Shet, Sridhar Epari, Alok Shetty, Saswata Saha, Hasmukh Jain, Manju Sengar, Carrie van der Weyden, H. Miles Prince, Ramzi Hamouche, Tinatin Muradashvili, Francine M. Foss, Marianna Gentilini, Beatrice Casadei, Pier Luigi Zinzani, Takeshi Okatani, Noriaki Yoshida, Sang Eun Yoon, Won Seog Kim, Girisha Panchoo, Zainab Mohamed, Estelle Verburgh, Jackielyn Cuenca Alturas, Mubarak Al‐Μansour, Josie Ford, María Elena Cabrera, Amy Ku, Govind Bhagat, Helen Ma, Ahmed Sawas, K. Kariya, Makoto Iwasaki, Forum Bhanushali, Owen A. O’Connor, Enrica Marchi, Changyu Shen, Devavrat Shah, Salvia Jain
Abstract
ABSTRACT: 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 natural killer-cell lymphomas (MTCL and MNKCL). We conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL. In peripheral T-cell lymphoma-not otherwise specified and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (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 years, primary refractory disease, histological subtype other than angioimmunoblastic T-cell lymphoma (AITL), extranodal sites >1, Ki67 ≥40%, and absolute lymphocyte count less than the lower limit of normal. A multivariable model incorporating these formed the basis for a prognostic index for R/R TCL, 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%, 23.3%, and 7%, 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 highlight continued efficacy of novel drugs globally and the potential of a new prediction model in informing heterogeneous prognosis within the R/R population of MTCL and MNKCL.