Abstract T082

Radiation-free initial treatment of early-stage favorable classic Hodgkin Lymphoma (RAFTING) trial: three-year follow-up

Background: The RAdiotherapy-Free Treatment for the INitial Therapy of Good-prognosis early-stage (RAFTING) classic Hodgkin Lymphoma (cHL) is a phase 2, multicenter, prospective study to assess feasibility and effectiveness of a risk-adapted therapy for early favorable cHL (efHL). The protocol is an example of a fully personalized medicine approach in a single-patient basis.

Methods: Untreated stage I–IIA efHL patients (p.), aged 18–70 years, without bulky, B-symptoms, or extranodal site, were stratified to high (HR), Low (LR) and very-low risk (VLR). HR p. had either or both risk factors (RF): total metabolic tumor volume (TMTV)  84 ml and/or a positive interim PET (PET-2). Very-Low risk (VLR) or Low-Risk (LR) p. were further identified by the absence/presence of one modified EORTC RF, in which bulky was replaced by a large nodal mass (LNM), with a largest diameter 5-10 cm. VLR and LR p. received 2 and 4 ABVD cycles respectively and HR p. 4 ABVD, INRT (20/30 Gy) + Nivolumab (N) 240 mg q2w, for ≤24 doses. VLR/LR p. with ABVD limited relapse (LIR) in initially involved ± up to 3 new nodal sites were rescued by INRT (36 Gy) and N x 24 q2w. Extended Relapse (ER) was considered a therapy failure requiring an off-study salvage. The primary study endpoint is a 3-Y PFS ≥85% in RT-free p., key 2nd endpoint: 3-Y event-free survival (EFS)-failure to planned treatment or death. All the PET/CT scans were centrally reviewed and TMTV measured with a 41% SUV threshold.

Results: Between 03/21 to 10/23, 174/180 (97%) stratified p. are evaluable in a per-protocol analysis as follows: 36 p. belonged to VLR, 89 to LR, and 49 to a HR group. Main RF in LR group were: LNM (49), age >50 (30), ESR >50 mm/h (28), and >4 nodal areas (25). Among HR pts, 35 had a high TMTV, 9 – positive PET-2, and 5 – both. 13 RT-free p. relapsed: 10 p. with LIR and 3 ER. 12 relapses occurred within the first 6 months. Ten p. were rescued per protocol and only 1 relapsed later after N. After a median follow-up of 35(5–60) months, 112 RT-free p. (90% of RT-free p., 64% of all p.) remained disease/RT-free. Two deaths (non-relapsed) and 3 secondary malignancies occurred. The 3-year PFS is 88.6%, with a one-sided 80% lower confidence bound of 86.2%, still above the predefined non-inferiority threshold of 85%. The 3-year EFS was 95.3% (95% CI, 91.8–98.9%).

Conclusion: The long-term results of the RAFTING trial confirm that a patient risk-adapted approach could cure >95% of the efHL with 64% being RT-free p.