Prognostic benefit of interim PET questioned in Hodgkin’s lymphoma
medwireNews: Interim positron emission tomography (PET) does not identify high-risk patients with advanced stage Hodgkin’s lymphoma who would benefit from the addition of rituximab to standard chemotherapy, research shows.
The team, led by Peter Borchmann (University Hospital of Cologne, Germany) found that patients with a positive PET after two cycles (PET-2) of standard chemotherapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) had similar progression-free survival (PFS) regardless of whether or not rituximab was subsequently added to their treatment regimen.
The multicenter, phase III German Hodgkin Study Group HD18 study included 1100 patients aged 18 to 60 years with newly diagnosed, advanced stage Hodgkin's lymphoma.
Of these, 440 had a positive PET-2, defined as ¹⁸F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake higher than the mediastinal blood pool (corresponding to Deauville scale 3), and were randomly assigned to receive six additional courses of either BEACOPPescalated alone or alongside rituximab (R-BEACOPPescalated).
At a median follow-up of 33 months, there was no significant difference in estimated 3-year PFS between the BEACOPPescalated and R-BEACOPPescalated groups, at rates of 91.4% and 93.0%, respectively.
There was also no difference in mortality, with six deaths reported in the BEACOPPescalated group and 10 in the R-BEACOPPescalated group, giving 3-year overall survival estimates of 96.5% and 94.4%, respectively.
The majority of patients (97–98%) in each group experienced at least one grade 3 or 4 adverse event, with common events including leukopenia (95% of the BEACOPPescalated group vs 96% of the R-BEACOPPescalated group) and severe infections (23 vs 20%).
Borchmann and co-researchers say the fact that PET-2 did not identify a high-risk cohort that would benefit from rituximab was unexpected and may be due to the fact that PFS was far better than expected, at over 90%.
Therefore, “[a]ny intervention is unlikely to improve this high proportion of patients achieving progression-free survival,” they write in The Lancet Oncology.
In an accompanying comment, Michael Crump, from the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, suggests that “the timing, conduct, and reporting of FDG-PET scans during chemotherapy,” could also have played a part.
“[A] high number of positive scans resulted in a greater number of favourable prognosis patients being included in the PET2-positive group randomly assigned to either the rituximab or standard group, reducing the event rate of this population compared with other trials,” he notes.
Borchmann et al conclude that, in their study, “a positive PET-2 finding does not necessitate any treatment modification.”
However, they accept that “the prognostic effect of PET-2 might be different depending on the treatment strategy used,” and “a negative PET-2 might still allow the reduction of chemotherapy in PET-2 negative patients.”
By Laura Cowen
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