The low‐risk early‐stage hodgkin lymphoma patients with inadequate response to chemotherapy. the preliminary experience from the rafting trial

Introduction: Early-stage Hodgkin Lymphoma (eHL) treated with a combined modality approach (CMT): chemotherapy (CT) and radiotherapy (RT) is a highly curable disease. However, for 70% of eHL patients (pts.) CT alone might be sufficient for cure. The RAFTING trial is a phase 2, multicenter, international prospective study investigating risk-adapted treatment strategy in eHL pts. We hypothesized that CT alone will be sufficient for to cure low-risk pts. Here we would like to present the clinical characteristics of low-risk pts. for whom CT was not sufficient to achieve a complete response (CR). Methods: Treatment intensity in RAFTING is tailored to two risk categories: low or high risk. Low-risk pts. are defined by low baseline metabolic tumor volume (MTV) and negative interim PET after 2 ABVD cycles. High-risk pts. were defined by high baseline MTV and/or positive iPET2. Within the low-risk group the pts. without any risk factors according to modified EORTC (mEORTC) criteria (largest nodal mass (LNM) 5–10 cm, Age > 50 yo, ESR > 50 mm/h, ≥4 nodal areas (NA)) (group 1a) are treated with 2 ABVD cycles only whereas pts. with at least 1 risk factor (group 1b)—with 4 ABVD cycles. High-risk pts. (group 3) receive “triple” therapy (4 ABVD cycles, RT and nivolumab for 12 months; RT-NIV). In case of “limited relapse” (i.e., within initially involved lymph nodes and/or up to 3 new nodal areas) pts. receive delayed RT-NIV. Results: In a per-protocol analysis, out of 77 stratified pts. in March 2023, seven pts. (9%) with low-risk disease, had inadequate response to ABVD alone (defined as achievement less than CR or early relapse (<6 months after the end of the CT): 2 pts. from group 1a and 5 pts. from group 1b. Specifically, one pt. from Group 1a had an extended and symptomatic (B symptoms) relapse, and underwent salvage therapy with ASCT and two pts. from group 1b were withdrawn due to PI decision. While 4 pts. (1 in Group 1a and 3 in Group 1b) with less than CR (2 pts.) or early relapse (2 pts.) received RT + NIV. The most frequent risk factor among 1b pts. was LNM, which was observed in 4 pts., age >50 yo—in 2 patients, and ≥4 NA—in 1 pt. More than 1 risk factor had 2 pts. In 4 cases the confirmatory biopsy was done and was positive for HL in 3 out of 4 cases. Conclusion: The frequency of inadequate response after CT alone observed in the RAFTING trial was similar to that reported by the literature. The most frequent adverse prognostic factor presented in these small pts. subset was a LNM. Keywords: combination therapies, Hodgkin lymphoma, radiation therapy No conflicts of interests pertinent to the abstract.