Reply: Interim PET in Hodgkin Lymphoma: Is It So Useless?

Abstract

More than 2,000 patients with advanced disease were included in 3 well-designed prospective trials, in which patients who-after 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-were PET-positive (Deauville score $ 4) were escalated to BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) whereas those who were PET-negative continued with the standard regimen (4 cycles of ABVD) (1-3). The PET positivity rate using this Deauville score as the cutoff was similar across these 3 studies, as was the outcome of both PET-positive and PET-negative patients. The study of the Southwest Oncology Group (1) enrolled 336 patients, 18% of whom were PET-positive. The "Response Adapted Therapy in Advanced Hodgkin Lymphoma" study (2) enrolled 1,119 patients, 25% of whom were PET-positive. The Italian GITIL/FIL HD0607 trial (3) enrolled 773 patients, 19% of whom were PET-positive. Overall, the 2-y progression-free survival of the PET-positive patients ranged between 64% and 67%. PET-negative patients who followed the standard regimen had a 2-y progression-free survival ranging between 82% and 89%, higher than the progression-free survival of the whole population.A major advantage of this strategy is that PET-negative patients (.80% of the total population) can be spared from the adverse effects of BEACOPP. As pointed out by Adams and Kwee, none of the interim 18 F-FDG PET/CT-adapted trials that have been performed so far had a control arm; that is, none continued standard ABVD in PET-positive patients. Apart from the fact that this arm would have been ethically difficult to defend, series have found 2-y progression-free survivals of 12%-27% in advanced-stage Hodgkin lymphoma patients PET-positive after 2 ABVD cycles-much lower than the 64%-67% found when these patients were intensified with BEACOPP (4,5), with this strategy therefore clearly having an advantage in improving outcome and decreasing the number of events. This finding was further confirmed by the results of the EORTC/LYSA/FIL H10 trial (6), which included 1,950 patients with early-stage Hodgkin lymphoma randomized between an experimental arm and a standard arm. Patients PET-positive after 2 ABVD cycles had a 5-y progression-free survival of 77.4% in the experimental arm that received standard ABVD plus involved-node radiotherapy, and survival improved to 90.6% in the experimental arm that received BEACOPP escalation plus involved-node radiotherapy (hazard ratio, 0.42; 95% confidence interval, 0.23-0.74; P 5 0.002).A deescalation trial (7) in 823 patients with advanced Hodgkin lymphoma (AHL2011 LYSA trial) has also recently confirmed the major role of an interim PET-guided strategy. Patients PETnegative after 2 BEACOPP escalations were moved to ABVD. Their progression-free survival was not inferior to that of the standard arm, in which BEACOPP was continued. Thus, deescalation avoids the toxic effect of BEACOPP while producing the same outcome.In view of the cited evidence, we strongly disagree with A...

Circulating tumor DNA in Hodgkin lymphoma

“…The lymphoma response to immunomodulatory therapy criteria (LYRIC) further refines response to immunomodulatory agents, such as checkpoint inhibitors [22]. Interim PET/ CT after two cycles of chemotherapy is a stronger predictor of outcome than any pretreatment prognostic factor; however, the exact positive and negative prognostic values in early and advanced stages are still under debate [23][24][25][26]. PET-adapted treatment strategies in early stages of HL tried to omit RT to reduce treatment-related toxicity.…”