Rituximab Intensification After Positive PET-2 Fails To Boost Advanced Hodgkin’s Lymphoma PFS

HD18 trial findings fail to show benefit for adding rituximab to chemotherapy in patients who have a positive interim positron emission tomography test after two cycles of BEACOPP escalated

medwireNews: Research suggests that intensifying chemotherapy with rituximab does not improve progression-free survival (PFS) in patients with advanced-stage Hodgkin’s lymphoma who have a positive positron emission tomography imaging test after two treatment cycles (PET-2).

After a median of 33 months, estimated 3-year PFS was 91.4% for the 219 patients who were randomly assigned to continue with a further six cycles of BEACOPPescalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) after their positive PET-2.

This was comparable to 93.0% for the 220 patients whose treatment was intensified to BEACOPPescalated plus rituximab 375 mg/m2 given on days 0 and 3 of cycle 4 and day 1 of cycles 5–8 (R-BEACOPPescalated).

Writing in The Lancet Oncology, the HD18 trial researchers describe the 3-year PFS in both groups as “much better than expected” and admit that “[a]ny intervention is unlikely to improve this high proportion of patients achieving progression-free survival.”

Indeed, commentator Michael Crump, from Princess Margaret Cancer Centre in Toronto, Ontario, Canada, writes that “these results exceed those recently reported for patients with a negative PET-2 after treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).”

Interim PET-2 was defined as positive where 18F-fluoro-2-deoxy-D-glucose uptake was higher than the mediastinal blood pool but below or equal to the liver, equivalent to Deauville scale 3, the team explains.

“Unexpectedly, a positive PET-2 after two courses of BEACOPPescalated did not identify a high-risk patient cohort in our phase 3 trial”, say Peter Borchmann, from the University Hospital of Cologne in Germany, and fellow German Hodgkin Study Group investigators.

“Accordingly, a positive PET-2 finding does not necessitate any treatment modification”, they believe.

However, 97% of patients in both treatment arms had grade 3 or 4 toxicity, the team reports.

Specifically, grade 3–4 leucopenia occurred in 95% and 96% of patients given BEACOPPescalated alone and with rituximab, respectively, with grade 3–4 severe infections reported in a corresponding 23% and 20%.

Grade 4 respiratory tract toxicity was the most frequent severe organ event, occurring in two (1%) and four (2%) of the BEACOPPescalated and R-BEACOPPescalated groups, respectively, while a second neoplasia was reported in seven (3%) and one (1%). Fatal treatment-related toxicity, namely infection, occurred in one (<1%) patient given BEACOPPescalated and three (1%) receiving R-BEACOPPescalated.

But the authors note that since the current HD18 trial began, the standard of care within the Germany Hodgkin Study Group has changed from eight to six cycles of BEACOPPescalated and this has “reduced the incidence of very severe sequelae such as acute treatment-related toxicity, which still shows a relevant impact on morbidity in our trial”.

And Michael Crump concludes that, in the absence of a reliable Biomarker for treatment escalation benefit, or a direct comparison of six cycles of intensified BEACOPPescalated versus treatment escalation only for patients with a positive PET-2 after two cycles of ABVD, “physicians and patients will continue to wrestle with the trade-off between better [PFS] but greater toxicity with the former approach and lower [PFS] but (possibly) less toxicity from the latter.”

References

Borchmann P, Haverkamp H, Lohri A, et al. Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin’s lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group. Lancet Oncol; Advance online publication 21 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30103-1

Crump M. Predicting outcomes after a positive interim FDG-PET scan in advanced Hodgkin’s lymphoma. Lancet Oncol; Advance online publication 21 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30085-2 

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