International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large studies evaluating outcomes for patients with scoring of immunoarchitectural patterns (IAPs) are needed. We performed an international study of pediatric and adult patients with all stages of NLPHL. Methods: Thirty-seven centers participated in the Global nLPHL One Working Group to retrospectively identify NLPHL cases from 1992-2021. 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 bootstrapping. Results: We identified 2,193 patients with a median age of 37 years (quartiles: 2-23, >23-37, >37-51, >51). Median follow-up was 6.3 years (IQR=3.5-10.8). Most had stage I-II disease (73.3%) and few B-symptoms (9.9%) or splenic involvement (5.1%). IAP was scored for 916 (41%), of which 73.8% were pattern A/B, 8.5% C, 9.0% D, 7.3% E, and 1.4% F. Frontline management included: chemotherapy alone (32.1%), combined modality therapy (30.9%), radiotherapy alone (27.4%), observation after excision (4.7%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 71.1%, 91.7%, 4.9%, and 3.2%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (HR=1.81, P<0.05). We developed the LP-IPS with 1 point each for age>45, stage III-IV, hemoglobin<10.5 g/dL, and splenic involvement. Increasing LP-IPS was associated (P <0.05) with worse PFS (HR=1.53) and OS (HR=2.34) as well as increased risk of lymphoma-specific death (HR=2.59) and transformation (HR=1.59). Conclusions:In this novel study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and may allow for deintensification of therapy for 97.3% of patients, regardless of variant pattern.Funding: : Jamie Flerlage received research support from the Lymphoma Research Foundation and the St. Jude Declaration of Interest: Kerry Savage: Honoraria/consulting: BMS, Merck, Gilead, Astra Zeneca, Janssen, Abbvie; Consulting: Celgene, Seagen; Steering committee: Beigene; DSMC: Regeneron Francisco Vega: "Receives research funding from CRISP Therapeutics, Allogene, and Geron corporation; Is supported by a R01CA222918 from the National Cancer Institute. Raphael Steiner: Research funding from Seagen, BMS, GSK and Rafael Pharmaceuticals Anca Prica: honoraria from Astra-Zeneca, Abbvie, Kite Gilead Pallawi Torka: Dipti Talaulikar: Research funding from Roche, Takeda and Jansen; Honoraria and board from Roche, Janssen, Beigene, Amgen, EUSA, CSL, and Antengene Dennis Eichenauer: honoraria from Takeda and Sanofi-Genzyme. Declare no competing interest.Ethical Approval: The paper approved by the Research Advisory Counsil of the Hospital.Sharing of data was also approved by the Research Advisory Counsil of the Hospital.The data collection was also approved by the Research Advisory Counsil of the Hospital.