P038 | RAFTING TRIAL: EARLY-STAGE FAVORABLE CLASSIC HODGKIN LYMPHOMA: RESULTS OF A FLEXIBLE INTENSITY APPROACH WITH CHEMO-RADIO-IMMUNOTHERAPY.

Background: RAFTING trial (NCT Id. 04866654) is a phase 2, prospective, international multicenter trial in nonbulky early (I-IIA) favorable Hodgkin Lymphoma (cHL), in which the Treatment (Tx) intensity is tailored to the risk of Tx failure in a single-patient (p.), in presence of any of the following risk factors (Rf): (a) ≥ 1 of the modified EORTC criteria, in which a Large Nodal Mass (LNM), with ∅ ≥ 5 cm in CT scan, replaces the classic bulky, (b) a high Total Metabolic Tumor Volume (TMTV) at baseline, (c) a positive interim PET after 2 ABVD (PET-2). Aims: Efficacy of a personalized Tx with ABVD alone in low-risk early cHL, with a 3-Y PFS, in a per protocol analysis (PP), ≥ 90%. Methods: Tx intensity is adapted in a single-patient basis to the risk of Txf in 3 p. groups: Gr 1 (low risk): PET-2 neg. & low TMTV p., without (Gr.1a) or with (Group 1b) ≥ 1 m-EORTC-Cr, treated with 2 or 4 ABVD cycles, respectively. After Complete Metabolic Response (CMR) entry, blood samples are drawn for cell-free tumor DNA assay. Gr 2: Gr 1 p. failing ABVD with a "limited relapse” (≤ 3 nodal areas: NA), addressed to Involved-node RT (36 Gy), and Nivolumab (N) 240 mg. i.v. twice in a month, for 6-12 months (Rt+N). Gr 3 (High risk): p. with a high TMTV or a positive PET-2 or both, treated with ABVD x 4 and Rt+N. Tx failure was defined as death or extended relapse (ER: >3 NA). PET/CT (and TMTV were centrally and blindly reviewed; TMTV was calculated with a 41% SUV threshold by 3 nuclear medicine experts. Results: 173/180 enrolled p. are valuable in PP: 124 (72%) were in Gr 1: 40 in Gr 1a (no Rf) and 84 in Gr 1b, with the following Rf prevalence: LNM (47), age >50 (28), ESR > 50 (27), > 4 NA (27). Forty-nine (28%) p. were in Group 3: 37 with a high TMTV, 8 with a PET-2+ and 4 with both. Overall, 10/124 (8%) Gr 1 p. failed ABVD: 9 switched to Rt+N (per protocol), 1 (Gr.1a) to ASCT (off study) showing an ER after PET-2; 16 out of 49 in Gr. 3 p. failed ABVD, one of them with ER, while 15 continued, per protocol, with Rt+N. One relapsed after Rt+N end. ABVD failure was recorded in 26 p.: in 20 after ABVD end (with a DS score 5 in 10), and +3 months after CR entry in 6. Overall, 58/173 (33%) p. received CT+RxT+Nivo Tx. After a median observation of 27 (18-49) months, the 2-y PFS in PP for all 173 p. was 98.9% (95% CI 95.5-99.7%), with 3 failures. Conclusions: in RAFTING trial a personalized-medicine approach was able to induce long-term disease control in 98.9% of the p.