Tailored Therapy in Hodgkin Lymphoma, Based on Predefined Risk Factors and Early Interim PET/CT: Israeli H2 Study
Authors: Dann Eldad J , Bairey Osnat , Bar-Shalom Rachel , Sabbag Elinor , Izak Marina , Korenberg Abraham , Akria Luiza , Attias Dina , Filanovsky Kalman , Abadi Uri , Ruchlemer Rosa , Abdah-Bortnyak Roxolyana , Goldschmidt Neta , Epelbaum Ron , Horowitz Netanel , Lavie David , Ben Yehuda Dina , Shpilberg Ofer , Paltiel Ora B. 
Published: October 2019

Abstract
Introduction: The aim of therapy in Hodgkin lymphoma (HL) is to maximize response and minimize long-term toxicity.
Methods: This multicenter study prospectively evaluated outcomes of HL patients (pts) recruited between 9/2006-8/2013, whose therapy was chosen according to baseline prognostic factors and tailored based on PET/CT results performed after 2 cycles of chemotherapy (PET-2). Pts with classic HL aged 18-60 years, stages I-IV were eligible. Those with early HL were categorized into early favorable (EFD) and unfavorable (EUD) disease groups. After 2 ABVD cycles, EFD pts with negative PET-2 underwent involved nodal radiation therapy (INRT) and EUD pts received 2 more ABVD cycles (total 4) followed by INRT. At physician's discretion, young pts requiring large-field irradiation could be given a total of 6 ABVD cycles with no RT. Pts with positive PET-2 received 2 additional ABVD cycles (total 4) in EFD and 4 additional cycles (total 6) in EUD followed by RT in both groups. Thus, differences in treatment modality between early disease pts with positive and negative PET-2 included addition of 2 ABVD cycles and mandatory RT for pts with positive PET-2.
Pts with advanced HL (B symptoms or stages III/IV) were assigned to therapy based on the International Prognostic Score (IPS). Standard-risk pts (IPS 0-2) initially received 2 ABVD cycles and those with IPS of ≥ 3 received 2 cycles of escalated BEACOPP (EB). If PET-2 was negative or showed minimal residual uptake in a single site, further therapy with 4 ABVD cycles was given and RT to bulky mediastinal masses was omitted. If PET-2 was positive with no evidence of HL progression, therapy was escalated to EB with RT given to bulky mediastinal masses.
Results: Data on 356 pts are presented in Table 1. At a median follow-up of 36 months (4-92), 3-y PFS for pts with early disease, overall, and for those with negative and positive PET-2, was 89, 91 and 74%, respectively (p=0.004). For pts with advanced HL, 3-y PFS overall and among those with negative and positive PET-2 was 85, 86 and 75%, respectively (p=0.012). No difference in PFS was observed according to IPS score. RT was given to 45% of pts with early and 12.5% of pts with advanced disease. Three pts died: one during autologous stem cell transplant (SCT), one after allogeneic SCT and one from acute myocardial ischemia.
Conclusions: Tailored therapy based on PET-2 is feasible both in early and advanced HL. A positive PET-2 is a marker of inferior prognosis both in early and advanced disease, even when therapy is escalated. For pts with advanced disease and high IPS, initiation of therapy with EB provides a higher rate of negative PET-2 than reported with ABVD. De-escalation of therapy is safe in advanced HL pts with negative PET-2 and does not affect the outcome. RT could be omitted in half of pts with early disease with no difference in PFS. Further follow-up is needed to draw conclusions regarding the long-term efficacy and safety of this personalized approach. Abstract 4409. Table N Pts with negative PET-2 N (%) Predictive value of PET-2Treatment adapted based on PET-2 Pts experiencing disease progression/relapseNPVPPVEscalation/ reductionN (%)Pos/NegPET-2Total356305(86)91%21%20/6146 (13)12/34Early disease173148 (85)92%32%10/018 (10)7/11Favorable2518 (75)94%16%6/02 (8)1/ 1Unfavorable148130 (88)92%37%4/016 (10)6/10Advanced183157 (86)85%22%10/6128 (15)5/23IPS 0-210694 (90)86%33%10/016 (15)3/13IPS ≥37763(81)84%14%0/6112 (15)2/10
PPV = Predictive value of positive PET-2 for relapse/progression

Disclosures
No relevant conflicts of interest to declare.