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