International Prognostic Score for Nodular Lymphocyte–Predominant Hodgkin Lymphoma
Authors: Binkley Michael Sargent , Flerlage Jamie E. , Savage Kerry J. , Akhtar Saad , Steiner Raphael , Zhang Xiao-Yin , Dickinson Michael , Prica Anca , Major Ajay , Hendrickson Peter G. , Hopkins David , Ng Andrea , Casulo Carla , Baron Jonathan , Roberts Kenneth B. , Al Kendi Jalila , Balogh Alex , Ricardi Umberto , Torka Pallawi , Specht Lena , De Silva Ravindu , Pickard Keir , Blazin Lindsay J , Henry Michael , Smith Christine M. , Halperin Daniel , Brady Jessica , Brennan Bernadette , Senchenko Maria Anatolevna , Reeves Marie , Hoppe Bradford S. , Terezakis Stephanie , Talaulikar Dipti , Picardi Marco , Kirova Youlia , Fergusson Paige , Hawkes Eliza A. , Lee Denise , Doo Nicole Wong , Barraclough Allison , Cheah Chan Y. , Ku Matthew , Hamad Nada , Mutsando Howard , Gilbertson Michael , Marconi Tamara , Viiala Nicholas , Maurer Matthew J , Eichenauer Dennis A , Hoppe Richard T. ,   on behalf of the GLOW Consortium, Borchmann Peter , Fuchs Michael , Hartmann Sylvia , Eich Hans Theodor , Lo Andrea C. , Skinnider Brian , Rauf M. Shahzad , Maghfoor Irfan , Pinnix Chelsea C. , Milgrom Sarah A , Vega Francisco , Alomari Mohammed , Collins Graham P. , Advani Ranjana H. , Metzger Monika L. , Wirth Andrew , Tsang Richard , Smith Sonali , Kelsey Christopher R. , McKay Pamela , Koenig Julie , Constine Louis S. , Sakthivel Ku G. , Plastaras John P. , Gao Sarah , Al Rahbi Nasser , Levis Mario , Sridhar Akshay , Shah Nimish , Osborne Wendy , Chang Isabela , Miall Fiona , Mikhaeel George , Penn Anthony , Volchkov Egor Vasilevich , Della Pepa Roberta , Northend Michael , Opat Stephen , Salvaris Ross , Tedjaseputra Aditya , Palese Monica , Shankar Ananth , Natkunam Yasodha , Kelly Kara M. 
Published: March 2024

PURPOSE Nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).