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Outcome-based interpretation of early interim PET in advanced-stage Hodgkin lymphoma

Carsten Kobe, Helen Goergen, Christian Baues, Georg Kuhnert, Conrad-Amadeus Voltin, Josée Zijlstra, Otto Hoekstra, Jasmin Mettler, Alexander Drzezga, Andreas Engert, Peter Borchmann and Markus Dietlein

Key Points

  • DS4 is recommended as the cutoff value for PET-2 positivity after 2 cycles eBEACOPP for advanced-stage HL.

Publisher's Note: There is a Blood Commentary on this article in this issue.

Abstract

The HD18 study for patients with newly diagnosed advanced-stage Hodgkin lymphoma (HL) used positron emission tomography (PET) after 2 cycles (PET-2) of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses (eBEACOPP) to guide further treatment. Here, we analyzed the impact of PET-2 results in the context of eBEACOPP according to the Deauville score (DS) in patients treated within the HD18 trial. Residual tissue was visually compared with reference regions according to DS. We analyzed the association between PET-2 uptake and baseline characteristics, progression-free survival (PFS), and overall survival (OS). One thousand five patients (52%) had DS1 or DS2, 471 (24%) had DS3, and 469 (24%) DS4. PET-2 uptake was associated with baseline risk factors large mediastinal mass, extranodal disease, and high International Prognostic Score (P < .0001 each). Among 722 patients receiving standard therapy with 6 cycles of eBEACOPP, 3-year PFS rates were 92.2%, 95.9%, and 87.6% with DS1-2, DS3, and DS4, respectively. Univariate hazard ratio (HR) for PFS in patients with DS4 vs DS1-3 was 2.3 (1.3-3.8; P = .002). DS4 was the only factor remaining significant for PFS in a multivariate analysis including the associated baseline risk factors. Three-year OS rates were 97.6% for DS1-2, 99.0% for DS3, and 96.8% for DS4, with a univariate HR for DS4 vs DS1-3 of 2.6 (1.0-6.6; P = .04). Residual uptake above that in the liver at PET-2 (ie, DS4) is an important risk factor regarding survival outcomes for patients treated with eBEACOPP upfront. We thus recommend DS4 as the cutoff value for PET-2 positivity. This trial was registered at www.clinicaltrials.gov as #NCT00515554.

  • Submitted May 17, 2018.
  • Accepted August 22, 2018.
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