Hasenclever International Prognostic Score (IPS) for advanced stage Hodgkin’s lymphoma

The International Prognostic Score (IPS) is used to stratify patients with advanced stage classical Hodgkin’s lymphoma using 7 risk factors into 6 prognostic groups.

The original score was developed from a retrospective review of clinical variables and disease outcomes in over 5000 patients with advanced classical Hodgkin’s lymphoma(1). Most patients were treated in the 1980s using either the MOPP or ABVD regimens. Using a Cox regression model the authors found that the 7 variables included in the final score had a similar negative impact on prognosis. Subsequently the IPS was validated by Moccia et al in a more modern patient series treated with ABVD between 1980 to 2010(2). The IPS remained prognostic for both freedom from progression (FFP) and overall survival (OS), however the outcomes for each prognostic group had narrowed reflecting improved outcomes with better implementation of the ABVD regimen.

The tool on this webpage reflects FFP and OS outcomes based on the Moccia et al 2012 study where all patients received the ABVD regimen.

International guidelines including NCCN and EORTC recommend recording the IPS score for patients newly diagnosed with advanced stage classical Hodgkin’s lymphoma. Patients with a IPS ≥3 have an inferior PFS and represent a potential population for more intensive/ novel treatment approaches, however consensus on this is not currently available.

The EORTC 20012 trial evaluated upfront BEACOPP (4 cycles of escalated-dose and 4 cycles of standard-dose) vs ABVD x8 in patients with IPS ≥3 advanced classical Hodgkin’s lymphoma. There was no improvement in OS (86.7% vs 90.3, respectively, at 4 years; P = .208) but a PFS benefit was reported in the initial report (83.4% vs. 72.8% for ABVD; P =.005) (3,4). However long-term follow-up failed to show a PFS advantage of escalated BEACOPP over ABVD(3).

The NCCN guidelines include as an option for selected patients with IPS ≥4 and age<60 to be treated with upfront escalated BEACOPP x2 followed by restaging PET and additional 4-6x escalated BEACOPP or A(B)VD x4 depending on Deauville score at interim PET(5,6). This has to be balanced against the increased toxicities both short and long term associated with escalated BEACOPP as compared with the ABVD regimen.

References:

1. Hasenclever D, Diehl V, Armitage JO, et al. A Prognostic Score for Advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506-1514. doi:10.1056/NEJM199811193392104
2. Moccia AA, Donaldson J, Chhanabhai M, et al. International Prognostic Score in Advanced-Stage Hodgkin’s Lymphoma: Altered Utility in the Modern Era. J Clin Oncol. 2012;30(27):3383-3388. doi:10.1200/JCO.2011.41.0910
3. Carde P, Karrasch M, Fortpied C, et al. Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(17):2028-2036. doi:10.1200/JCO.2015.64.5648
4. Carde PP, Karrasch M, Fortpied C, et al. ABVD (8 cycles) versus BEACOPP (4 escalated cycles => 4 baseline) in stage III-IV high-risk Hodgkin lymphoma (HL): First results of EORTC 20012 Intergroup randomized phase III clinical trial. J Clin Oncol. 2012;30(15_suppl):8002. doi:10.1200/jco.2012.30.15_suppl.8002
5. Borchmann P, Plütschow A, Kobe C, et al. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(2):223-234. doi:10.1016/S1470-2045(20)30601-X
6. Casasnovas R-O, Bouabdallah R, Brice P, et al. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2019;20(2):202-215. doi:10.1016/S1470-2045(18)30784-8