The International Prognostic Factor Project Score (IPS) in Advanced Stage Hodgkin Lymphoma Has Limited Utility in Patients Treated in the Modern Era.
Authors: Moccia Moccia A. , Donaldson Jane , Chhanabhai Mukesh , Hoskins Paul , Klasa Richard , Savage Kerry J. , Shenkier Tamara , Skinnider Brian , Gascoyne Randy D. , Connors Joseph M. , Sehn Laurie H. 
Published: October 2019

Abstract
Abstract 1554
Poster Board I-577

Introduction
The International Prognostic Factor Project Score (IPS) is the most widely utilized risk stratification index for Hodgkin lymphoma (HL) (Hasenclever, N Engl J Med, 1998). Based on patients treated before 1992, it incorporates 7 adverse risk features (male gender, age ≥45 y, stage IV, hemoglobin <105 g/L, WBC ≥15 × 109/L, lymphocyte count <0.6 × 109/L or <8% of differential, albumin <40 g/L) and predicts for a 5-year freedom-from progression (FFP) ranging from 42-84%.The IPS has not been validated in a more recently treated population, where more accurate pathologic diagnosis, routine use of growth factors and enhanced supportive care may have improved outcomes compared with historic results.

Methods
This retrospective population-based analysis used the British Columbia Cancer Agency Lymphoid Cancer Database to identify all patients ages 15-65 y diagnosed from January 1st,1990 to June 30th, 2008 with advanced stage HL (stage III/IV, or stage I/II with B symptoms or bulky disease ≥10 cm), who were treated with curative intent with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or an ABVD-equivalent regimen and had complete information including all IPS variables. Primary endpoint was FFP, defined as the interval from diagnosis to first progression or relapse or death due to treatment toxicity; deaths from unrelated causes were censored.

Results
579 patients were identified. Median age was 29 y (range 15-65); 11 (2%) stage I, 239 (41%) stage II, 202 (35%) stage III and 127 (22%) stage IV; 245 (42.3%) had bulky disease; and 359 (62%) had B symptoms. Histologies included: 455 (79%) nodular sclerosing, 35 (6%) mixed cellularity, 7 (1%) lymphocyte-rich, 11 (2%) lymphocyte depleted, 13 (2%) nodular lymphocyte predominant, 58 (10%) HL NOS. 161 (28%) patients received IFRT with primary treatment. Adverse prognostic factors were present as follows: 119 (21%) age≥45, 375 (65%) albumin <40 g/L, 88 (15%) WBC ≥15 × 109/L, 116 (20%) hemoglobin <105 g/L, 57 (10%) lymphocyte count <0.6 × 109/L or <8%, 302 (52%) male, 127(22%) stage IV. Only 37 (6.4%) patients had a prognostic score ≥5. With a median follow-up of 73 months (range, 1-222), 512 (88.4%) patients were alive and 67 (11.6%) had died (39 with HL, 7 due to toxicity and 21 from unrelated causes). Five year FFP and overall survival (OS) were 79% and 91%, respectively. The IPS was prognostic for both FFP (p=.0035) and OS (p<.0001), with 5-y FFP ranging from 66% to 86% and 5-y OS ranging from 74% to 98% (Table 1). In univariate analysis only stage IV (p=.003) and hemoglobin (P=.001) were prognostic for FFP. Albumin (p=.054), age (p=.082) and WBC (p=.094) were borderline significant, but gender (p=.329) and lymphocyte count (P=.496) appeared to have a weaker prognostic value for FFP. Only stage IV (HR=1.63, CI 1.10-2.40, p=.014) and hemoglobin (HR=1.73, CI 1.17-2.57, p=.006) were prognostic for FFP in a multivariate Cox regression.

Conclusion
The IPS remains prognostic for patients with advanced stage HL treated in a more modern era. However, it does not identify risk groups with sufficiently good or poor outcome to justify deviation from standard therapy. Identification of truly low or high risk populations will require supplementation with molecular markers and/or the use of early PET scanning. Caution should be used when comparing results from current clinical trials to historic controls, since more recent outcomes with standard therapy are clearly superior to those previously reported.

Disclosures
No relevant conflicts of interest to declare.