Top Line: Is PET-adaptive therapy a safe option for patients with bulky early stage Hodgkin lymphoma?
The Study: There have been several trials establishing PET-adaptive therapy for early stage HL. In patients with unfavorable disease, the challenge has been to maintain good outcomes for those with a good response and improve outcomes for those with residual disease. Back in 2021, the randomized, phase 3 HD17 trial found that PET-adaptive treatment for early stage, unfavorable HL resulted in non-inferior 5-year progression free survival while allowing two-thirds of patients to omit radiation. In HD17, all patients received an intensified chemotherapy regimen of ABVD x 2 + eBEACOPP x 2 prior to PET. CALGB 50801 was a small, non-randomized trial that evaluated a PET-adaptive approach in 94 patients who specifically had bulky (>10cm or >⅓ intrathoracic diameter) stage I/II HL. They received 2 cycles of ABVD followed by a restaging PET. The majority of patients (78%) had a negative PET (Deauville 1-3), and they received 4 more cycles of ABVD. This was a chemo de-intensification of sorts from regimens such as HD17 where all unfavorable patients received eBEACOPP. Those with a positive PET received 4 cycles of eBEACOPP and 30.6 Gy involved field radiation (IFRT). At 3 years, the PFS rate was 93.1% in the negative PET group and 89.7% in the positive PET group. The trial was underpowered, but the PFS rate in the positive PET arm was deemed to be not significantly worse than the negative PET arm. Nevertheless, the question in an adaptive trial is not so much the positive PET intensification arm as it is the outcomes of the de-intensified arm. Those appeared favorable in CALGB 50801’s bulky disease population and comparable to the outcomes of the broader unfavorable HL populations in the RATHL and H10 trials.
TBL: The outcomes of PET-adaptive therapy for unfavorable, early stage HL appear to hold true for the subset of patients with bulky disease. | LaCasce, J Clin Oncol 2022