Summary The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I–IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3‐negative patients received no further therapy. PET3‐positive patients received three additional cycles of ABVD plus involved‐field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re‐evaluated by PET scan (PET6). Study endpoints were 3‐year progression‐free survival (PFS) and overall survival (OS) rates. Two hundred and thirty‐nine patients with early‐stage and 138 with advanced‐stage were evaluable. Overall, 260 patients (70%) were PET3‐negative and had higher 3‐year PFS (90% vs. 65%; P < 0·0001) and OS (98% vs. 92%; P = 0·007) rates than PET3‐positive patients. All PET3‐negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90–91%; P = 0·76) and OS (97–99%). The only independent prognostic factor for PFS was PET3‐negativity (Hazard ratio 3·8; 95% confidence interval 2·4–6·3; P < 0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.

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PET CT adapted treatment for first line Hodgkin Lymphoma has been widely studied in the last decades. Long-term follow-up is important to judge both efficacy and safety of this approach.Patients and Methods: We analyzed updated follow-up data on all patients (pts.) treated within the LH-05 GATLA trial. Newly diagnosed pts. with HL Stages I-IV were included. All patients received 3 ABVD and were evaluated with a PET-CT (PET-CT+3). Pts. with a negative PET-CT+3 (DS 1 and 2) were considered in metabolic CR and received no further therapy. Pts with DS 3 and 4 completed 6 ABVD and IFRT on PET-CT positive areas. Pts with progressive disease (DS 5) after 3 ABVD received salvage chemotherapy. With a median age of 35 yrs., 300 presented with localized stage and 190 with advanced stage. Results:In LH-05 of all pts. 338 (69%) achieved CR with negative PET-CT+3, 152 (31 %) were PET-CT+3 positive. With a median follow up of 120 months the EFS and OS for all pts. at 5 years is 79.2% and 94.3% respectively. Pts with negative PET-CT+3 had an EFS of 89% and 80% for localized and advanced stage, compared to 63% for 276 -SUPPLEMENT ABSTRACTS all pts. with positive PET-CT+3 (p < 0.0001). We perform a multivariate analysis for EFS which included age, stage, IPS, bulky disease, extranodal areas and the result of the PET+3. This last parameter together with age were the only ones with statistical significance (p = 0.001 and 0.046 respectively). Stage at diagnosis was not significant.With long term follow up the OS at 5 years is 97.3% and 87.3% for all PET+3 negative vs PET+3 positive pts.When comparing the results LH-05 with our previous clinical trial (LH-96) there is no difference in EFS and OS at 5 years but in LH-05 only 31% received more than 3 cycles of ABVD and IFRT compared to 61% and 100% in LH-96. This PET adapted approach reduces exposure to chemo and radiotherapy with no negative effect on long term outcome. Conclusion:This long term follow up data support the PET-CT adapted approach for all stages of HL after a short course of ABVD. In the Cox regression model, PET-CT at completion of treatment was the most significant factor associated to EFS.Treatment with 3 cycles of ABVD can be adequate for pts. with negative PET-CT+3 regardless their stage at diagnosis. Nevertheless, this long term follow up demonstrated that there is still room for improvement trying to identify PET-CT+3 negative patients that will relapse and escalating treatment in PET-CT+3 positive patients to improve outcome. GATLA is designing a trial with the aim to improve these two different risk groups.