Page 170 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 6b
remained higher during further treatment.However,this did not translate into better short- or long-term outcome for the complete study population. Also, exploratory subgroup analyses for different age groups, age-adjusted IPI risk groups, and sexes could not identify any subgroup that might benefit from rituximab intensification. Our randomized phase III study differs in some essential aspects from the phase II studies. The study populations were not comparable; in our study, both young and elderly patients with DLBCL were included, whereas the phase II studies included elderly patients only and included a broader spectrum of aggressive B-cell lymphoma diagnoses. In our phase III study, staging and response evaluation was based on PET-CT, whereas it was based on CT scanning only in the phase II studies. Lastly, the schedules for rituximab intensification differed to some extent. However, from these studies, it may be concluded that dose-intensification within a standard R-CHOP regimen is insufficient to improve outcome for patients with DLBCL. Tout et al [19] demonstrated that rituximab exposure is influenced by baseline metabolic tumor volume (MTV) and suggest that outcome might improve when the rituximab dose is individualized according to the MTV. This interesting hypothesis needs to be confirmed in a prospective trial.
For the past 2 decades, R-CHOP has remained the standard treatment for previously untreated DLBCL, and it has proven exceedingly difficult to improve on this baseline [20]. To date, neither next-generation anti-CD20 monoclonal antibodies, such as obinutuzumab or ofatumumab, nor approaches adding targeted therapy based on molecular subtypes of DLBCL, such as bortezomib, ibrutinib, or lenalidomide in ABC/non-GCB subgroups, have proven successful [ 6,21-24]. More recent developments in chemo-immunotherapy using antibody- drug conjugates (eg, polatuzumab vedotin), bispecific antibodies (eg, anti-CD3 × anti-CD20), immune checkpoint inhibitors, and CAR T-cell therapy may reveal new opportunities, and novel insights into DLBCL biology may provide essential information for meaningful patient selection for such treatments [25,26]. Our phase III study shows that early rituximab intensification in patients with untreated DLBCL during R-CHOP-14 does not improve outcome.
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