The overwhelming majority of patients with early-stage unfavorable Hodgkin lymphoma may no longer require radiotherapy to treat their disease, according to data presented during the virtual edition of the 25th European Hematology Association (EHA) Annual Congress.1
The findings of the randomized, phase III, HD17 trial have shown that omission of radiotherapy does not compromise 5-year overall survival in a cohort of patients with early-stage Hodgkin lymphoma who responded well to standard chemotherapy. Positron-emission tomography (PET)-guided treatment using a backbone of standard chemotherapy was noninferior to combined-modality treatment with chemotherapy and consolidation radiotherapy. Omission of radiotherapy was associated with very low treatment-related toxicity, the study authors reported.
“These data confirm that most patients with early-stage unfavorable Hodgkin lymphoma can be treated with a brief but highly effective chemotherapy regimen alone,” said Peter Borchmann, MD, Associate Medical Director of the Department of Hematology and Head of Lymphoma Program at the University Hospital of Cologne, Germany. “This strategy has no relevant Hodgkin lymphoma or treatment-related mortality and thus achieves 5-year overall survival that does not differ from that of the healthy German population.” The Co-Chairman of the German Hodgkin Study Group added: “This is the first time we have seen this finding in one of our studies.”
“These data confirm that most patients with early-stage unfavorable Hodgkin lymphoma can be treated with a brief but highly effective chemotherapy regimen alone.”— Peter Borchmann, MD
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Long-Term Risks With Radiotherapy
As Dr. Borchmann reported, previous data from the HD14 study demonstrated superior 5-year progression-free survival with intensified chemotherapy (two cycles of escalated BEACOPP [bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone] followed by two cycles of ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine]) compared with just four cycles of ABVD.2 Although the intensified approach is more toxic in terms of accrued acute hematologic toxicity and infections, noted Dr. Borchmann, important endpoints such as treatment-related mortality, secondary primary malignant neoplasms, and fertility for both men and women were no different than with four cycles of ABVD. However, use of radiotherapy consolidation raises concern about long-term sequelae in young patients.
“We already know we cannot reduce radiotherapy when we use ABVD alone as the backbone without compromising progression-free survival, but we hypothesized that the more effective ‘two plus two’ chemotherapy regimen might allow the omission of radiotherapy from the treatment concept in patients who achieve a complete metabolic response,” Dr. Borchmann said.
For this multicenter, international phase III trial, Dr. Borchmann and colleagues randomly assigned patients (18 to 60 years of age) with early-stage unfavorable Hodgkin lymphoma to combined-modality treatment with intensified chemotherapy followed by 30 Gy of involved-field radiotherapy, or PET-guided treatment, omitting radiotherapy in patients with PET4-negative disease (Deauville score < 3). The investigators aimed first to show noninferiority of the PET4-guided strategy in a per-protocol analysis regarding progression-free survival with a noninferiority margin of 8% and second to confirm PET4 positivity as a risk factor for progression-free survival in an intention-to-treat analysis of patients receiving combined-modality treatment.
Survival Rates Similar to Those in Cancer-Free Population
As Dr. Borchmann reported, the investigators enrolled 1,100 patients between January 2012 and March 2017. Of the 979 patients with confirmed PET4 results, 651 patients (66.5%) had PET4-negative disease, 238 patients (24.3%) had a Deauville score of 3, and 90 patients (9.2%) had a Deauville score of 4.
With a median observation time of 46 months, 5-year progression-free survival was 97.3% in patients receiving standard treatment vs 95.1% in the PET-stratified arm—for a difference of just 2.2%.
“We can safely conclude that PET-stratified treatment is noninferior to the combined modality,” said Dr. Borchmann. He also noted the sensitivity analysis of patients with PET4-negative disease showed even higher percentages of progression-free survival and an even smaller difference between arms (1.7%).
With a median observation time of 47 months, 5-year overall survival rates were virtually identical between the two groups. Patients receiving standard treatment had an overall survival of 98.8% at 5 years, whereas patients randomly assigned to PET-stratified treatment had an overall survival of 98.4%.
“We had just 10 fatal outcomes in this very large study,” said Dr. Borchmann, who noted that 2 patients died of Hodgkin lymphoma and 1 patient died of treatment-related mortality. “This is an extremely low rate of death overall, and it’s important to note the death rate for this trial cohort is no different from that in the normal German population control.”
“With this PET-guided treatment strategy, we have almost eliminated toxicity of Hodgkin lymphoma as a reason for death,” Dr. Borchmann added.
Findings also showed that patients with a Deauville score of 4 alone were associated with poorer outcomes, confirming previous results from HD16 and HD18 trials.
“With a 5-year progression-free survival of 81%, a Deauville score of 4 or more after standard treatment indicates a relevant risk for treatment failure,” said Dr. Borchmann. “Future development should focus on the earlier identification of these patients who might do better with more intensive systemic treatment or a different treatment altogether. For patients who respond well to chemotherapy, however, PET-guided omission of radiotherapy is the new standard of care for the German Hodgkin Study Group,” Dr. Borchmann concluded.
DISCLOSURE: Dr. Borchmann reported no conflicts of interest.
1. Borchmann P: 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 Congress. Abstract S101.
2. Skoetz N, Will A, Monsef I, et al: Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev 5:CD007941, 2017.
Stephen M. Ansell, MD, PhD, Professor of Medicine in the Department of Hematology at the Mayo Clinic, Minnesota, underscored the importance of the HD17 trial results. “These data show, in a randomized fashion, that a PET-directed approach when using more intensive chemotherapy allows for the...