Individualized PET4-Guided Treatment Allows Omission of Radiotherapy for Patients With Hodgkin Lymphoma

After use of a common chemotherapy treatment for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma, PET4-negativity allowed certain patients to omit consolidation radiotherapy without clinically impacting efficacy results, according to data published in The Lancet Oncology.

In the phase 3, multicenter, randomized German Hodgkin Study Group HD17 trial (NCT01356680), the 2 + 2 chemotherapy regimen was used, which was defined 2 cycles of escalated doses of etoposide, cyclophosphamide, and doxorubicin with regular doses of bleomycin, vincristine, procarbazine, and prednisone (eBEACOPP) plus 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy.

“Individualised PET4-guided treatment after 2 + 2 chemotherapy allows omission of radiotherapy in most patients with newly diagnosed early-stage unfavourable Hodgkin lymphoma,” wrote the investigators. “PET-guided therapy therefore substantially reduces the proportion of patients at risk of late effects from irradiation.”

For patients in the standard combined-modality treatment group, the 5-year progression-free survival rate was 97.3% (95% CI, 94.5%-98.7%) versus 95.1% (95% CI, 92.0%-97.0%) for patients in the PET4-guided treatment group (HR, 0.523; 95% CI, 0.226-1.211). The median follow-up for this analysis was 46.2 months (IQR, 32.7-61.2).

A total of 1100 patients were randomly assigned to either the standard combined-modality treatment group (n = 548) or the PET4-guided treatment group (n = 552) between January 13, 2012, and March 21, 2017.

The safety profile featured common grade 3 or 4 acute hematological adverse events including leucopenia (83% of the standard treatment group vs 84% of the PET4-guided treatment group) and thrombocytopenia (26% vs 33%, respectively). The most common grade 3 or 4 acute nonhematological adverse events were infection (6% vs 8%) and nausea/vomiting (7% vs 6%). More, common acute radiotherapy-associated adverse events included dysphagia (6% vs 2%) and mucositis (2% vs 0%).

Overall, 29% of patients in the combined-modality treatment group reported 229 total serious adverse events reported, while 30% of patients in the PET4-guided treatment group reported a total of 235 serious adverse events.

“Omission of consolidation radiotherapy shortens the overall treatment duration in patients with early-stage unfavourable Hodgkin lymphoma and eliminates late effects potentially arising from radiotherapy,” wrote the investigators. “The survival outcomes of patients in our study compare favourably with any data from controlled trials published thus far.”

The primary end point of the research was progression-free survival, with a focus on showing non-inferiority for the PET4-guided strategy. Non-inferiority was defined as a difference of 8% when analyzing the 5-year progression-free survival data of the 2 groups.

The research team acknowledged the many limitations of this research, specifically citing the inability to evaluate any potential late effects of radiotherapy due to the possibility that these can happen more than 20 years after treatment. As a result, it was difficult to quantify the benefits of omitting this treatment, suggesting that the benefit of omitting radiotherapy may be smaller than initially estimated.

“This new treatment strategy could be applicable to clinical practice, where the medical infrastructure allows administration of eBEACOPP chemotherapy and assessment of metabolic response by [18F-flurodeoxyglucose]-PET,” wrote the investigators.

Reference:

Borchmann P, Plutschow A, Kobe C, et al. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2021;22(2):223-234. doi:10.1016/S1470-2045(20)30601-X