PET-stratification can omit radiotherapy in early-stage unfavourable Hodgkin lymphoma

Data from the HD17 trial indicate that PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavourable Hodgkin lymphoma (HL) should be the new standard of care.

Dr Peter Borchmann (University Hospital of Cologne, Germany) presented the HD17 study, on behalf of the German Hodgkin Study Group (GHSG) [1]. The standard of care for early-stage HL with risk factors indicating an unfavourable prognosis (“early-stage unfavourable HL”) consists of 4 cycles of chemotherapy [2x BEACOPPescalated (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) and 2x ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)] followed by 30Gy radiotherapy. However, late sequalae such as cardiovascular disease and secondary malignancies

are a matter of concern for this combined modality treatment (CMT). HD17 aimed to investigate whether radiotherapy can be omitted from the CMT for patients that respond well to chemotherapy, as determined by FDG-PET, and demonstrate the efficacy of an individualised approach to treatment.

A total of 1,100 early-stage unfavourable HL (Stage I-II, with ≥1 risk factor) patients were randomised; Arm A received 2 cycles BEACOPPescalated plus 2 cycles ABVD followed by 30Gy Involved-Field Radiotherapy irrespective of FDG-PET results after chemotherapy, and Arm B received 2 cycles BEACOPPescalated plus 2 cycles ABVD followed by 30Gy Involved-Node Radiotherapy if FDG-PET was positive after chemotherapy, or 2 cycles BEACOPPescalated plus 2 cycles ABVD with a treatment stop if FDG-PET was negative after chemotherapy. The primary endpoint of HD17 was non-inferiority of Arm B in regards of progression-free survival (PFS), and key secondary endpoints were overall survival (OS) and the rate of patients achieving a complete remission (CR/CRu) at final restaging after completion of study treatment.

The primary endpoint was met. With a median observation time of 46 months, PFS for Arm A was 97.3% (95% CI 94.5-98.7), and for Arm B was 95.1% (95% CI 92.0-97.0) demonstrating non-inferiority for the PET-stratified Arm B (difference PFS 2.2 months; P=0.12). Likewise, OS at 47 months follow-up was also the same between the arms (Arm A 98.8%, 95% CI 96.7-99.6 vs Arm B 98.4%, 95% CI 96.2-99.3).

In summary, the HD17 trial has proven that omission of radiotherapy does not result in a loss of tumour control in patients responding well to a standard chemotherapy regimen. The vast majority of early stage unfavourable HL patients can be treated with the brief and highly effective 2+2 chemotherapy alone. The overall efficacy in this trial was extremely high. At 5 years follow-up, only 2 out of 1,100 patients died from HL and a single patient died from treatment emerging adverse events. The mortality of patients with early stage unfavourable HL in the HD17 study did not differ from the normal German population. PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavourable HL could be the new standard of care.

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   1. Borschmann P, et al. 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. EHA25 Virtual, 11-21 June 2020, Abstract S101.

Posted on 9 September 202019 November 2021