PET-based response assessment in Hodgkin lymphoma patients undergoing PD-1 blockade: data of the German Hodgkin Study Group NIVAHL trial for early unfavorable stages

Ziel/Aim The NIVAHL trial recently demonstrated excellent progression-free survival and unexpectedly high complete response rates to nivolumab with either concomitant or sequential doxorubicin, vinblastine, and dacarbazine (AVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma (HL). However, established response criteria may not accurately reflect the early therapeutic effects of programmed cell death protein 1 (PD-1) antibodies, particularly in treatment-naïve patients. We therefore examined the potential of novel positron emission tomography (PET) biomarkers in this setting.

Methodik/Methods From April 2017 through October 2018, a total of 110 treatment-naïve patients with HL were recruited for the randomized, multicenter phase II NIVAHL trial. In the present analysis, we included all 59 individuals with PET images available to the central review panel for quantitative assessment before April 30, 2019. Patients in arm A and B underwent restaging after 2 courses of AVD with 2 concomitant nivolumab infusions per cycle (N-AVD) and 4×nivolumab, respectively. Besides conventional criteria, our analysis considered parameters such as metabolic tumor volume (MTV) or total lesion glycolysis (TLG) and their change under treatment (delta-MTV and delta-TLG) for early response evaluation.

Ergebnisse/Results At interim restaging, PET showed a mean delta-MTV and delta-TLG of -99.8 % each in patients from arm A undergoing 2×N-AVD, compared to -91.4 % and -91.9 %, respectively, for treatment group B, which was assigned to 4×nivolumab upfront. This marked decrease in MTV and TLG was observed regardless of the initial tumor burden.

Schlussfolgerungen/Conclusions Our study revealed that anti-PD-1-based first-line treatment leads to rapid near-complete reduction of tumor metabolism in early-stage unfavorable HL. Hence, PET-derived biomarkers could facilitate individualized immunotherapy and allow reduction or even omission of chemo- and radiotherapy in selected patients.

Publication History

Article published online:
08 April 2021