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Early metabolic response determination by FDG-PET allows substantial reduction of chemotherapy and its toxicity in patients with advanced stage Hodgkin lymphoma

The results of the GHSG HD18 study demonstrated that reduced therapy with 4 cycles of eBEACOPP was non-inferior to 6/8 cycles in terms of 5-year progression-free survival for advanced stage Hodgkin lymphoma (HL) patients with a negative PET-2. No treatment related mortality in the experimental group was observed and moreover patients had fewer infections, less organ toxicities and a very low incidence of second acute myeloid leukemia. Overall, this resulted in a significantly superior 5-year overall survival for the patient cohort with reduced treatment.

Hodgkin lymphoma is the most common malignancy of young adults. Intensive chemotherapy with 8 or 6 cycles of eBEACOPP is very effective in patients with advanced-stage HL, albeit at the expense of severe toxicities. Aiming at better tolerability, Borchmann and colleagues investigated whether metabolic response determined by positron emission tomography (PET-2) after two cycles of eBEACOPP would allow to select patients who could be treated with reduced intensity (4 cycles of eBEACOPP) without loss of efficacy.

PET-2 was centrally assessed with FDG uptake not higher than the mediastinal blood pool defined as negative. Patients with negative PET-2 were randomly assigned to receive 6 or 2 additional cycles (i.e. 8 or 4 cycles of eBEACOPP in total, respectively). PET-positive residues after chemotherapy were irradiated. Based on the results of the previous HD15 trial, the protocol was amended in June 2011 and the standard therapy was reduced from 8 to 6 cycles of eBEACOPP in total. The trial was designed to exclude inferiority of 6% or more of the experimental treatment (4 cycles of eBEACOPP) compared with the pooled standard treatment (8 or 6 cycles of eBEACOPP) at 5 years.

In total 2.101 patients were enrolled. 1.005 patients with negative PET-2 were randomly assigned to either 8/6 cycles of eBEACOPP (n=504) or 4 cycles of eBEACOPP (n=501). With a median follow-up of 55 months, estimated 5-year PFS in the per-protocol set was 91.2% (88.5-94.0) with 8/6 cycles of eBEACOPP and 91.8% (89.0-94.6) with 4 cycles eBEACOPP (difference +0.6%, 95% CI -3.3 - 4.5, excluding the non-inferiority margin of -6%). Estimated 5-year overall survival (OS) in the per-protocol set was 95.4% (93.4-97.4) with standard eBEACOPP, and 97.6% (96.0-99.2) with 4 cycles of eBEACOPP (p = 0.006).

In the standard arm, 95% of patients had at least one acute hematological toxicity of grade 3-4 compared with 90% in the experimental arm, including severe infections in 75 (15%) and 40 (8%) patients, respectively. Acute severe organ toxicities were documented for 91 (18%) and 38 (8%) patients, respectively. 25 patients (5%) in the standard group (8/6 cycles of eBEACOPP) and 9 patients (2%) in the experimental group (4 cycles of eBEACOPP) died; most frequent cause of death was second malignancy (11 and 1 patient, respectively). No patient in the experimental group died from treatment-related toxicities.

In conclusion, metabolic response assessment using FDG-PET after 2 cycles of eBEACOPP allows the reduction of therapy with 8/6 to only 4 cycles without loss of efficacy as determined by PFS in advanced-stage HL patients. Furthermore, the abbreviated treatment with 4 cycles of eBEACOPP is associated with improved tolerability and consequently leads to a significant OS benefit over standard therapy. Thus, PET-guided reduced therapy with eBEACOPP combines good efficacy with high safety. Borchmann and colleagues therefore recommended this treatment strategy for advanced-stage HL patients.


P. Borchmann, H. Goergen, C. Kobe. Treatment reduction in patients with advanced-stage Hodgkin lymphoma and negative interim PET: final results of the international, randomized phase 3 trial HD18 by the German Hodgkin study group. EHA 2017, oral presentation, abstract S150.


Speaker Peter Borchmann


Prof. Peter Borchmann, MD, PhD, University Hospital of Cologne, Cologne, Germany


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