Omitting Radiation Does Not Reduce Survival for Patients with Early Unfavorable HL

Radiation therapy can be omitted in patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma (HL) without sacrificing efficacy, according to data presented at the virtual 25th Congress of the European Hematology Association.

Results from the HD17 trial show that omission of radiotherapy does not result in a loss of tumor control in patients responding well to a standard chemotherapy regimen and reduces the proportion of patients at risk for adverse events related to radiation, according to Peter Borchmann, MD, department of Internal Medicine, University Hospital of Cologne, Cologne, Germany, and co-chairman of German Hodgkin Study Group (GHSG).

In the standard combined-modality treatment (CMT) group (n = 428), 5-year progression-free survival (PFS) was estimated at 97.3% (95% CI, 94.5-98.7) compared with 95.1% (95% CI, 92.0-97.0) in the positron emission tomography after 4 cycles (PET4)-guided treatment group (n = 477). Five-year overall survival (OS) rates were 98.8% (95% CI, 96.7-99.6) in the standard CMT group and 98.4% (95% CI, 96.2-99.3) in the PET4-guided group.

Investigators concluded that the vast majority of early stage unfavorable HL patients can be treated with the brief and highly effective 2+2 chemotherapy alone. PET-guided 2+2 chemotherapy has become the new standard of care at GHSG.

The international phase 3 HD17 trial (NCT01356680) looked at whether an individualized approach for patients with early unfavorable HL could be used, omitting consolidation radiotherapy (RT) in patients who respond well to chemotherapy as determined by PET.

Patients were designated as having early unfavorable HL if they had clinical stage I or stage II disease and one or more of the following risk factors: B symptoms. (fever ≥38°C, soaking night sweats, weight loss ≥10% within 6 months).

In general, patients received 4 to 6 cycles of chemotherapy followed by involved-site radiation therapy. CMT comprising of chemotherapy and RT has been standard of care for patients with early-stage unfavorable Hodgkin lymphoma. But the use of radiotherapy in younger patients raises concerns about adverse events, such as cardiovascular disease and secondary malignancies.

In the trial, patients where given the German Hodgkin Study Group standard 2+2 regimen comprised of 2 cycles of eBEACOPP and 2 subsequent cycles of ABVD.

Patients aged 18 to 60 years were assigned to CMT with 4 cycles of chemotherapy followed by 30 Gy involved-field RT or PET-guided treatment. RT was omitting in PET4-negative patients (Deauville score, <3). The endpoints were 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 confirmation PET4-positivity as risk factor for PFS in an intention-to-treat analysis of CMT-treated patients.

The study enrolled 1100 patients from January 2012 to March 2017. Of 979 patients with confirmed PET4 result, 651 (66.5%) were PET4-negative, 238 (24.3%) had Deauville score of 3, and 90 (9.2%) Deauville score 4. The median observation time for PFS was 46 months and 47 months OS.

Overall, HL mortality rates were low. At 5 years of follow-up, there were only 10 fatalities in the trial; 2 patients died from HL and 1 died of adverse events related to treatment. Non-inferiority of the PET-guided arm was confirmed in PET-negative patients, with 5-year PFS of 95.1% (95%-CI, 92.0-91.0).

Sensitivity subgroup analysis in PET4-negative patients (PP, n = 597) confirmed non-inferiority with an estimated 5-year PFS of 97.7% (95% CI, 93.6-99.2) in the CMT group, and 95.9% (95% CI, 92.4-97.9) in patients treated without RT in the PET4-guided group (difference -1.7%; 95% CI, –5.3 to 1.8).

The difference was more pronounced when Deauville score 4 was used as cut-off for positivity; 5-year PFS rates were 81.6% (95% CI, 67.9-89.9) for Deauville score 4 patients versus 98.1% (95% CI, 95.9-99.1) in Deauville score 1-3 patients.

Reference

Borchmann P. PET-guided therapy allows omission of radiotherapy in early-stage unfavorable Hodgkin lymphoma. Presented at: the 25th Annual European Hematology Congress. June 11-21, 2020. Abstract #S101.