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566 Metabolic Tumor Volume after Two Cycles of Chemotherapy in Patients Treated for Advanced-Stage Hodgkin Lymphoma: Analysis of the German Hodgkin Study Group Phase III HD18 and HD21 Trials

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Optimization of Therapy
Hematology Disease Topics & Pathways:
Research, Clinical trials, Hodgkin lymphoma, Lymphomas, Clinical Research, Diseases, Lymphoid Malignancies, Technology and Procedures, Measurable Residual Disease , Imaging
Sunday, December 8, 2024: 12:15 PM

Justin Ferdinandus, MD1,2*, Helen Kaul, Dipl.-Math.3,4*, Gundolf Schneider, MSc1,4*, Michael Fuchs, MD1,4*, Hans Theodor Eich, MD1,5*, Christian Baues, MD1,6*, Johannes Rosenbrock, MD1,7*, Katrin S Roth, MD8*, Alexander Drzezga8*, Lutz Van Heek8*, Markus Dietlein1,8*, Peter Borchmann, MD1,2 and Carsten Kobe, MD1,8*

1German Hodgkin Study Group, Cologne, Germany
2University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, and Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Cologne, Germany
3German Hodgkin Study Group (GHSG), Cologne, Germany
4Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
5Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany
6Department of Radiation Oncology, University Hospital of Ruhr-Universität Bochum, Marien Hospital Herne, Herne, Germany
7Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
8Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany

Introduction:

PET-guided treatment is standard of care to treat patients diagnosed with advanced-stage classical Hodgkin Lymphoma (AS-cHL) in several countries. Here, we investigate the role of metabolic tumor volume (MTV) for the response assessment of patients treated for AS-cHL.


Methods:

The investigator-initiated phase III trials HD18 (NCT00515554) and HD21 (NCT02661503) randomized patients between 18-60 years with newly diagnosed AS-cHL to receive BEACOPP (HD21 standard arm, HD18) or BrECADD (HD21 experimental arm). All patients received two cycles of chemotherapy followed by response assessment after two cycles (PET-2). MTV after two cycles (MTV-2) encompassed all lymphoma tissue with standard uptake value > 4. To exclude confounding of PET-guided treatment, we first analyzed MTV-2 in patients treated in control arms of HD18 who received 6 cycles of BEACOPP irrespective of PET-2 (C6-Cohort). Cox-regression models and Kaplan Meier estimates were used to analyze impact of MTV-2 on progression-free survival (PFS). Findings were validated in the full ITT cohorts of HD18 and HD21.


Results:

A total of 645 patients were included in the C6-Cohort, of these 471 (64.6%) were rated as DS1-3 in PET-2 and 569 (88.2%) had no residual MTV-2. Compared to patients with DS1-3 (5y-PFS 93.5%; CI95: 91.2-95.9), Patients with measurable MTV-2 had significantly inferior PFS (5y-PFS 77.5%; HR 3.62, CI95: 1.94-6.76), while patients without detectable MTV-2 and DS4 had similarly high PFS (5y-PFS 89.3%; HR 1.65; CI95: 0.8-3.38). In line with these results, in the analyzed ITT cohorts of HD18 (n = 1756) and HD21 (n= 1211), patients with DS4 but with completely resolved MTV-2 had similar outcomes as patients with DS1-3 (HD18: HR 1.12, CI95: 0.69-1.80; HD21: HR 1.03, CI95: 0.55-1.95), whereas patients with measurable MTV-2 featured higher risk of progression (HD18: HR 2.98, CI95: 1.92-4.64; HD21: HR 4.44, CI95: 2.78-7.09). Results were similar in both trial arms of HD21 (BEACOPP vs. BrECADD) and frequency of measurable MTV-2 was similar in HD18 post-amendment and HD21.

Conclusion:

Complete resolution of MTV after two cycles of first-line chemotherapy for AS-cHL occurs in a vast majority of patients and associates with favorable prognosis, irrespective of DS. Approximately 10% had measurable MTV-2 (i.e. any lesion with SUV > 4) and face high risk of progression. Our results advocate implementation of quantitative biomarkers to refine response assessment in AS-cHL.

Disclosures: Ferdinandus: Roche Pharma: Honoraria; Takeda Oncology: Honoraria. Borchmann: Takeda Oncology, MSD, Incyte: Research Funding; Takeda Oncology, BMS, Roche, MSD, Celgene, Miltenyi Biotech, Gilead, Abbvie: Honoraria; Takeda Oncology, BMS, Roche, Amgen, Miltenyi Biotech, Gilead, MSD: Consultancy.

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