-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

925 PET-Guided Treatment of Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase 3 Trial HD16 By the German Hodgkin Study Group

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Hodgkin Lymphoma: Chemotherapy and Response Adapted Approaches
Hematology Disease Topics & Pathways:
Diseases, Therapies, Non-Biological, Hodgkin Lymphoma, chemotherapy, Lymphoid Malignancies
Monday, December 3, 2018: 4:30 PM
Room 6F (San Diego Convention Center)

Michael Fuchs1*, Helen Goergen2*, Carsten Kobe, MD3*, Hans Eich, MD4*, Christian Baues, MD5*, Richard Greil, MD6, Stephanie Sasse, MD2*, Josée M Zijlstra, MD7*, Andreas Lohri, MD8*, Andreas Rosenwald9*, Bastian von Tresckow, MD10*, Volker Diehl, MD11, Georg Kuhnert12*, Markus Dietlein, MD3*, Peter Borchmann, MD13 and Andreas Engert, MD14

1German Hodgkin Study Group (GHSG), Department I of Internal Medicine, First department of Internal Medicine / German Hodgkin Study Group (GHSG), Cologne, Germany
2German Hodgkin Study Group (GHSG), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
3Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany
4Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany
5Department of Radiooncology and Cyberknife Center, University Hospital Cologne, Cologne, Germany
6Paracelsus Medical University Salzburg and Salzburg Cancer Research Institute on behalf of the AGMT Study Group, Salzburg, Austria
7Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands
8Onko-Praxis Bethesda, Birsfelden, Switzerland
9Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany
10German Hodgkin Study Group (GHSG), Department I of Internal Medicine, Department I of Medicine, Center of Integrated Oncology Cologne-Bonn, Cologne, Germany
11German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany
12Nuklearmedizin Siegen / Kreuztal, Siegen, Germany
13German Hodgkin Study Group (GHSG), Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany
14German Hodgkin Study Group (GHSG), Department I of Internal Medicine, University Hospital of Cologne Dept. of Internal Medicine I, Koeln, Germany

Background. Combined modality treatment (CMT) consisting of two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and 20 Gy of involved-field radiotherapy (IFRT) is widely accepted standard of care for early-stage favorable Hodgkin lymphoma (HL). Recent clinical research suggests that metabolic response assessment after two cycles of chemotherapy using FDG-PET (PET-2) can predict the individual outcome and PET-2 negativity might allow reducing the overall treatment intensity.

Aims. We assessed whether omitting consolidating radiotherapy in patients with negative PET-2 is feasible without loss of efficacy as determined by progression-free survival (PFS). Furthermore, we analyzed the prognostic impact of PET-2 among patients receiving CMT.

Methods. Between November 2009 and December 2015, we recruited patients with newly diagnosed, early-stage favorable HL aged 18–75 years from Germany, Switzerland, Austria, and the Netherlands for this double-blind, randomized, parallel-group phase 3 trial. Patients were randomly assigned to receive standard CMT with 2x ABVD and 20 Gy IFRT or PET-guided treatment, whereby IFRT was restricted to those patients with a positive PET after 2xABVD. PET-2 was centrally assessed by a panel blinded towards the randomization result, with FDG uptake not higher than the mediastinal blood pool (i.e., Deauville score 1-2) defined as negative. The trial was designed to exclude inferiority of 10% or more in 5-year PFS of ABVD only compared with CMT in a per-protocol analysis among PET-negative patients, corresponding to a non-inferiority margin of 3.01 for the hazard ratio, and to detect a 5-year PFS difference of 5% or more between PET-2-positive and -negative patients receiving CMT, each with 80% power.

Results. A total of 1150 patients were enrolled; 628 patients with negative PET-2 were eligible for the per-protocol non-inferiority analysis and were treated with CMT (n=328) or ABVD alone (n=300). With a median follow-up of 47 months, the estimated 5-year PFS was 93.4% (90.4–96.5) with CMT and 86.1% (81.4–90.9) with chemotherapy only (difference 7.3%, 95% CI 1.6%–13.0%). The hazard ratio was 1.78 with a 95% CI ranging from 1.02 to 3.12, including the non-inferiority margin of 3.01. The PFS difference primarily resulted from a significant increase in disease recurrences with in-field recurrence rates of 2.1% vs. 8.7% (p=0.0003); there was no relevant difference regarding out-field recurrences (3.7% vs. 4.7%, p=0.55). Estimated 5-year overall survival in the per-protocol population was 98.1% (96.5–99.8) with CMT and 98.4% (96.5–100.0) with ABVD.

693 patients assigned to receive CMT were eligible for the analysis of the PET objective and had a negative (n=353) or positive (n=340) PET-2. With a median follow-up of 46 months, estimated 5-year PFS was 93.2% (90.2–96.2) among PET-2-negative and 88.1% (83.8–92.3) among PET-2-positive patients (p=0.035). When using the more common liver cutoff (Deauville score 4) for the definition of PET-2 positivity, the difference was more pronounced (5-year PFS 93.1% [90.7%–95.5%] vs. 80.1% [71.2%–88.9%], p=0.0004).

Conclusion. In early-stage favorable HL, radiotherapy cannot be safely omitted from standard CMT without a clinically relevant loss of tumor control in patients with negative PET-2. PET positivity after 2xABVD represents a risk factor for PFS in HL patients treated with standard CMT, particularly when a Deauville score of 4 is considered as cutoff for positivity.

Disclosures: Greil: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Sandoz: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. von Tresckow: MSD: Honoraria, Other: Travel support, Research Funding; Novartis: Honoraria, Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding. Borchmann: Novartis: Consultancy, Honoraria.

Previous Abstract | Next Abstract >>
*signifies non-member of ASH