POSITRON EMISSION TOMOGRAPHY GUIDED OMISSION OF RADIOTHERAPY IN EARLY-STAGE UNFAVORABLE HODGKIN LYMPHOMA: FINAL RESULTS OF THE INTERNATIONAL, RANDOMIZED PHASE III HD17 TRIAL BY THE GHSG
Author(s):
Peter Borchmann
Affiliations:
Department I of Internal Medicine ,University Hospital of Cologne,Cologne,Germany
EHA Library. Borchmann P. 06/12/20; 294921; S101
Prof. Dr. Peter Borchmann
Prof. Dr. Peter Borchmann
Contributions
Abstract
This abstract is embargoed until Friday, June 12, 08:30 CEST.

Abstract: S101

Type: Presidential Symposium

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Presidential Symposium

Background

Aims
Combined-modality treatment (CMT) comprising of chemotherapy and consolidation radiotherapy (RT) is standard of care for patients with early-stage unfavourable Hodgkin lymphoma (HLeu). However, the use of RT raises concern about long-term sequelae in this young patient cohort. We thus asked in the HD17 study, whether RT can be omitted in patients achieving a complete metabolic response after “2+2” chemotherapy (2x eBEACOPP followed by 2x ABVD) without loss of efficacy.

Methods
Patients aged 18 to 60 years with newly diagnosed, HLeu were included in this international, randomized phase III trial. Patients were assigned to CMT with 4 cycles of chemotherapy followed by 30Gy involved-field RT or PET-guided treatment, omitting RT in PET4-negative patients (DS, Deauville score, <3). The German Hodgkin Study Group (GHSG) standard CTx is the “2+2” regime comprising of 2 cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and subsequent 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). We aimed first to show non-inferiority of the PET4-guided strategy in a per protocol analysis regarding progression-free survival (PFS) with a non-inferiority margin of 8% and second to confirm PET4-positivity as risk factor for PFS in an intention-to-treat analysis of CMT-treated patients.

Results
Between January 2012 and March 2017, we enrolled 1,100 patients. Of 979 patients with confirmed PET4 result, 651 (66.5%) were PET4-negative, 238 (24.3%) had DS3, and 90 (9.2%) DS4. Median observation time was 45 months (95%>CI, 43 – 47) for PFS and 47 months (95%>CI, 46 – 49) for overall survival (OS). In the standard CMT group (PP, n=428), 5-year PFS was estimated at 97.3% (95% CI, 94.5% to 98.7%), as compared to 95.1% (95% CI, 92.0% to 97.0%) in the PET4-guided treatment group (PP, n=477). The 5-year PFS difference between the two groups was -2.2% (95%>CI, -5.3% to 0.9%), excluding the lower margin of -8%. Sensitivity subgroup analysis in PET4-negative patients (PP, n=597) confirmed non-inferiority with an estimated 5-year PFS of 97.7% (95%>CI, 93.6% to 99.2%) in the CMT group, and 95.9% (95%>CI, 92.4% to 97.9%) in patients treated without radiotherapy in the PET4-guided group (difference -1.7%, [95%>CI, -5.3% to 1.8%]). In the CMT/CTx+RT group (n=646), 5-year PFS was estimated at 94.2% (95%>CI, 90.1% to 96.6%) for PET4 positive patients (n=328) as compared to 97.6% (95%>CI, 94.0% to 99.9%) for PET4-negative patients (n=318). The Hazard ratio for the difference was 3.03 (95% CI, 1.1% to 8.3%) confirming PET4 as significant risk factor. The difference was more pronounced when DS4 was used as cut-off for positivity: 5-year PFS rates were 81.6% (95%>CI, 67.9% to 89.9%) for DS4 patients versus 98.1% (95%>CI, 95.9% to 99.1%) in DS1-3 patients. 5-year overall survival rates (ITT) were 98.8% (95%>CI, 96.7% to 99.6%) in the standard CMT group and 98.4% (95%>CI, 96.2% to 99.3%) in the PET4-guided group. So far, 10 fatal events have occurred in HD17 including two HL-related events and one treatment-related death.

Conclusion
PET4-negativity after treatment with “2+2” chemotherapy in patients with newly diagnosed early-stage unfavourable HL allows omission of consolidation RT without relevant loss of efficacy. PET-guided therapy thereby reduces the proportion of patients at risk for late effects from irradiation.

Session topic: 17. Hodgkin lymphoma - Clinical

Keyword(s): Hodgkin's lymphoma, PET

This abstract is embargoed until Friday, June 12, 08:30 CEST.

Abstract: S101

Type: Presidential Symposium

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Presidential Symposium

Background

Aims
Combined-modality treatment (CMT) comprising of chemotherapy and consolidation radiotherapy (RT) is standard of care for patients with early-stage unfavourable Hodgkin lymphoma (HLeu). However, the use of RT raises concern about long-term sequelae in this young patient cohort. We thus asked in the HD17 study, whether RT can be omitted in patients achieving a complete metabolic response after “2+2” chemotherapy (2x eBEACOPP followed by 2x ABVD) without loss of efficacy.

Methods
Patients aged 18 to 60 years with newly diagnosed, HLeu were included in this international, randomized phase III trial. Patients were assigned to CMT with 4 cycles of chemotherapy followed by 30Gy involved-field RT or PET-guided treatment, omitting RT in PET4-negative patients (DS, Deauville score, <3). The German Hodgkin Study Group (GHSG) standard CTx is the “2+2” regime comprising of 2 cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and subsequent 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). We aimed first to show non-inferiority of the PET4-guided strategy in a per protocol analysis regarding progression-free survival (PFS) with a non-inferiority margin of 8% and second to confirm PET4-positivity as risk factor for PFS in an intention-to-treat analysis of CMT-treated patients.

Results
Between January 2012 and March 2017, we enrolled 1,100 patients. Of 979 patients with confirmed PET4 result, 651 (66.5%) were PET4-negative, 238 (24.3%) had DS3, and 90 (9.2%) DS4. Median observation time was 45 months (95%>CI, 43 – 47) for PFS and 47 months (95%>CI, 46 – 49) for overall survival (OS). In the standard CMT group (PP, n=428), 5-year PFS was estimated at 97.3% (95% CI, 94.5% to 98.7%), as compared to 95.1% (95% CI, 92.0% to 97.0%) in the PET4-guided treatment group (PP, n=477). The 5-year PFS difference between the two groups was -2.2% (95%>CI, -5.3% to 0.9%), excluding the lower margin of -8%. Sensitivity subgroup analysis in PET4-negative patients (PP, n=597) confirmed non-inferiority with an estimated 5-year PFS of 97.7% (95%>CI, 93.6% to 99.2%) in the CMT group, and 95.9% (95%>CI, 92.4% to 97.9%) in patients treated without radiotherapy in the PET4-guided group (difference -1.7%, [95%>CI, -5.3% to 1.8%]). In the CMT/CTx+RT group (n=646), 5-year PFS was estimated at 94.2% (95%>CI, 90.1% to 96.6%) for PET4 positive patients (n=328) as compared to 97.6% (95%>CI, 94.0% to 99.9%) for PET4-negative patients (n=318). The Hazard ratio for the difference was 3.03 (95% CI, 1.1% to 8.3%) confirming PET4 as significant risk factor. The difference was more pronounced when DS4 was used as cut-off for positivity: 5-year PFS rates were 81.6% (95%>CI, 67.9% to 89.9%) for DS4 patients versus 98.1% (95%>CI, 95.9% to 99.1%) in DS1-3 patients. 5-year overall survival rates (ITT) were 98.8% (95%>CI, 96.7% to 99.6%) in the standard CMT group and 98.4% (95%>CI, 96.2% to 99.3%) in the PET4-guided group. So far, 10 fatal events have occurred in HD17 including two HL-related events and one treatment-related death.

Conclusion
PET4-negativity after treatment with “2+2” chemotherapy in patients with newly diagnosed early-stage unfavourable HL allows omission of consolidation RT without relevant loss of efficacy. PET-guided therapy thereby reduces the proportion of patients at risk for late effects from irradiation.

Session topic: 17. Hodgkin lymphoma - Clinical

Keyword(s): Hodgkin's lymphoma, PET

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