Abstract T049

Factors driving treatment intensity in the whole cohort of patients with early-stage favorable (I-IIA), nonbulky Hodgkin Lymphoma enrolled in the RAFTING trial (NCT 04866654).

Background: The treatment (Tx) of early-stage Hodgkin Lymphoma (eHL) with Chemotherapy plus Radiotherapy (RT) is offset by a 40-year cumulative incidence of 2nd malignancy ≥ 45%. RAFTING is a phase 2, prospective, clinical trial in nonbulky eHL (I-IIA) in which Tx intensity (Tx-I) is tailored to the risk of Tx failure (Txf) in a single patient (p.), depending on: (a) presence of ≥ 1 of the modified EORTC criteria (m-EORTC-Cr), in which bulky is replaced by a Large Nodal Mass (LNM): a nodal mass with a diameter ≥ 5 cm in baseline CT/PET/CT, (b) a high Total Metabolic Tumor Volume (TMTV) at baseline, (c) a positive PET, at interim (PET-2) or after ABVD (EoC-PET). Aims: To assess the prevalence of old and new risk factors (Rf) to drive Tx-I in nonbulky eHL.

Methods: In RAFTING trial Tx-I is adapted to risk of Txf in 3 groups of p.: Gr 1 (low risk): PET-2 neg. & low TMTV p., without (Gr.1a) or with ≥ 1 m-EORTC-Cr (Group 1b), treated respectively with 2 or 4 ABVD cycles. After CR entry, blood samples are shipped every 3 months to Bellinzona (CH) for cell-free tumor DNA assay. Gr 2: Gr 1 p. with a post-ABVD "limited relapse” (</= 3 nodal areas), or failing CR, treated with Involved-node RT (36 Gy), and Nivolumab (N) 240 mg. e.v. twice in a month, for 6-12 months (Rt+N). Gr 3 (High risk): p. with a positive PET-2 or a high TMTV or both, treated with ABVDx4 and Rt+N (Triplet-T). The main study endpoint is a 3-Y PFS ≥ 90% in Group1 p. All PET/CT scans are reviewed by an expert panel, and TMTV measured with a SUV threshold of 41%.

Results: out of 180 p. enrolled from 03.2021 till 10.2023, 174 are valuable in a per-protocol analysis: 125 (72%) in Gr 1: 40 in Gr 1a and 85 in Gr 1b. The prevalence of Rf in Gr 1b was: LNM (48), age >50 (29), ESR > 50 (23), > 4 nodal areas (19). The Rf in 49 (28%) Gr 3 p. were PET-2+ (9), High TMTV (36), and both (4). Overall, after a median f-up of 380 days, 12/125 (13%) Gr 1 p. failed ABVD: 11 switched to Rt+N (per protocol), 1 to ASCT (off protocol); In Gr 3, 11/49 p. failing ABVD continued, per protocol, with Rt+N. Overall, the most frequent Rf for Txf was a LNM (13/23), and most ABVD failures occurred in EoC PET (19, with a DS score 5 in 11), or +3 months after CR entry (4).

Conclusions: In a personalized-medicine approach, LNM and TMTV at baseline were able to drive Tx-I in half (88/174) of p. (Figure1). Triplet-T was given to 72/174 (41%) p.: in 49 (28%) as frontline Tx, while Rt+N was given to 23 (13%) as ABVD fail rescue.

Authors

Jan Maciej Zaucha, Marco Picardi, Kateryna Filonenko, Manuel Gotti, Javier Nunez, Andrea Rossi, Eva Domingo-Domènech, Agnieszka Giza, Roberto Sorasio, Andrea Visentin, Mariana Bastos, Ewa Paszkiewicz-Kozik, Ramon Garcia-Sanz, Caterina Patti, Stephane Chauvie, Fabrizio Bergesio, Luca Guerra, Anna Sureda, Andrea Gallamini