Tailored Therapy In Hodgkin Lymphoma, Based on Predefined Risk Factors and Early Interim PET/CT, Can Lead to Modification and Safe Reduction In Therapy: Results of 134 Patients on the Israel National Hodgkin Study.
Authors: Dann Eldad J. , Bairey Osnat , Bar-Shalom Rachel , Izak Marina , Korenberg Abraham , Akria Luiza , Attias Dina , Filanovsky Kalman , Abdach Liana , Goldschmidt Neta , Epelbaum Ron , Rowe Jacob M. , Yehuda Dina Ben , Shpilberg Ofer , Paltiel Ora B. 
Published: October 2019

Abstract
Abstract 2809
The current aim of treatment for Hodgkin lymphoma (HL) is to maximize response and minimize long term toxicity. This study prospectively evaluates the outcome of patients with HL whose therapy is chosen based on baseline prognostic factors and is tailored based on results of PET/CT imaging performed after 2 cycles of chemotherapy. In this multicenter study, initiated in 2006, we reduce the intensity of therapy for early responders and escalate the intensity for those with suboptimal early response. Patients with classic HL aged 18–60 years, I-IV are eligible. Those with early disease are categorized according to the German Hodgkin study group criteria for early favorable and unfavorable disease. Following 2 cycles of ABVD, patients with early favorable disease and a negative PET/CT undergo involved nodal radiation therapy (INRT) and those with early unfavorable disease receive 2 more cycles of ABVD (total of 4 cycles) followed by INRT. Patients whose interim PET/CT remains positive are given 2 additional cycles of ABVD for a total of 4 or 6 cycles followed by radiation therapy. Patients with advanced disease including all those with B symptoms or stages III and IV are assigned treatment according to the International Prognostic Score (IPS). Standard risk patients (IPS score 0–2) are initially treated with 2 cycles of ABVD and those with IPS score of ≥ 3 receive 2 cycles of escalated BEACOPP (EB). If interim PET/CT is negative or shows minimal residual uptake in no more than a single site then further therapy with 4 cycles of ABVD is administered and radiation therapy to bulky mediastinal mass is omitted. If interim PET/CT is positive but there no evidence of disease progression then therapy is escalated to EB with radiation therapy given to bulky mediastinal mass. 153 patients enrolled, of which 134 reached their interim imaging. Table 1 shows the number of patients in each risk group, positive predictive value of interim positive PET/CT and negative predictive value of negative study. Six patients had disease progression, two of them had primary refractory disease. One patient succumbed during autologous bone marrow transplantation. After a short follow up, median 20 month (6-50), the current study appears to demonstrate progression free survival (PFS) of 95%. The negative predictive value for the patient with negative interim study was 96% demonstrating that de-escalation is feasible and safe for patients with interim negative imaging. Further follow up and a larger cohort is needed to draw conclusions regarding the PFS of patients with interim positive PET/CT study as well as the long term toxicity.
Table 1. Risk group score n Positive interim PET/CT Negative interim PET/CT Progression Total Progression Total No Progression All patients 152 18 2 118 114 6 (4%)     Early favorable 15 2 0 6 6 0     Early unfavorable 70 2 1 55 53 3 (4%) Advanced disease 67     Score 0–2 38 2 0 31 29 2 (5%)     Score ≥3 29 6 1 20 20 1 (3%)

Disclosures:
No relevant conflicts of interest to declare.