PET-2 Negativity Allows Treatment De-Escalation In Advanced Hodgkin’s Lymphoma Patients

Phase III trial results support the use of four cycles of the polychemotherapy eBEACOPP regimen in advanced-stage Hodgkin’s lymphoma patients with a negative positron-emission tomography result after two cycles

medwireNews: An additional two cycles of the intensive eBEACOPP regimen are sufficient for patients with newly diagnosed advanced-stage Hodgkin’s lymphoma who have a negative positron-emission tomography scan after two cycles (PET-2), suggest the results of the German Hodgkin Study Group HD18 trial.

The researchers note in The Lancet that PET-2-guided de-escalation “substantially reduced the treatment-related risks and at the same time improved the overall survival [OS] for early-responding patients” and they, therefore, “strongly recommend” this treatment approach in the advanced-stage setting.

Patients enrolled in the phase III trial underwent PET screening after receiving two cycles of the polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses), following which those with a negative result (Deauville score of 1 or 2) were randomly assigned to receive either two (four in all) or six (eight in all) additional cycles. The team explains that a protocol amendment partway through, after the HD15 trial results established six cycles of eBEACOPP as the standard regimen, led to control participants recruited thereafter receiving just four further cycles (total six).

A per-protocol analysis showed that the 5-year progression-free survival (PFS) rate did not differ significantly between the 474 patients in the four-cycles group and the 446 controls who received either eight or six cycles, at 92.2% and 90.8%, respectively, and the 95% confidence intervals did not contain the prespecified noninferiority margin of –6%.

Lead investigator Peter Borchmann, from the University Hospital of Cologne in Germany, and colleagues report that OS was significantly improved in the four-cycles versus the control group, with corresponding 5-year rates of 97.7% and 95.4%.

Furthermore, patients who received four cycles of eBEACOPP were less likely to experience severe infections and organ toxicities than their counterparts given the control regimen, at incidence rates of 8% versus 15% and 8% versus 18%, respectively.

The survival findings were similar in a subgroup analysis including just the control patients enrolled after the protocol change, with respective 3-year PFS and OS rates of 94.6% and 98.8% in the four-cycles arm compared with 91.8% and 97.5% for those who received six cycles. However, the difference in OS rates was not statistically significant in this case.

The study authors point out that the results are “not yet finally conclusive owing to short follow-up”, but add that the findings “remain important also when 6 × eBEACOPP is regarded as the standard to be challenged.”

Commentator Maja Maraldo, from the University of Copenhagen in Denmark, applauds the researchers for “their continued effort”, but adds that questions arise in the light of the HD18 trial results. Specifically, can the results be extrapolated to patients with a PET-2 Deauville score of 3 and are four cycles as effective as six for those with a Deauville score of 4?

“These questions should be formally tested, as the medical community is now left to speculate whether the maximum effect of upfront eBEACOPP is achieved with only four cycles”, she concludes.


Borchmann P, Goergen H, Kobe C, et al. PET-guided treatment in patients with advanced-stage Hodgkin’s lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet; Advance online publication 20 October 2017. doi:

Maraldo MV. Continued conundrum of PET-CT and Hodgkin’s lymphoma. Lancet; Advance online publication 20 October 2017. doi:

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