23 | RADIOTHERAPY IMPROVES PROGRESSION‐FREE SURVIVAL FOR STAGE IA NLPHL: A RETROSPECTIVE REPORT FROM THE GLOBAL NLPHL ONE WORKING GROUP (GLOW)

Introduction: Management of stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) varies due to insufficient evidence-based data secondary to the rarity of disease. Unique from cHL, NLPHL has a persistent relapse risk 5–20 years post-treatment that may not be mitigated with intensification of frontline therapy. We evaluated treatment outcomes for patients with stage IA NLPHL in a large retrospective GLOW (Global NLPHL One Working Group) study. Methods: The retrospective cohort includes 2243 patients diagnosed with NLPHL from 1992 to 2021 treated at 38 international institutions. Patients with treatment details (n = 2138) were analyzed according to stage, excision status, and LP-IPS risk factors. We used Kaplan-Meier to measure progression-free survival (PFS) and overall survival (OS). Outcomes of management strategies were compared. Results: The cohort of 779 patients with stage IA had male predominance (74%) and median age of 35 years at diagnosis (range: 3–89). Median follow-up was 6.1 years with median time to progression of 3.3 years. The 6-year PFS and OS for the whole cohort were 86.3% and 97.7%, respectively. Group A, with complete excision (n = 152; 19.5%), had a 6-year OS of 98.4% and 6-year PFS of 74.9%. Those with observation alone (n = 99) had a significantly lower 6-year PFS of 65.5% versus 90.5% for those who received radiotherapy (RT) (n = 53) (p ≤ 0.001). In group B, with measurable NLPHL, rituximab (n = 31), RT alone (n = 325), ABVD (n = 40) and ABVD+RT (n = 130) were the most commonly utilized. Outcomes for ABVD or rituximab alone were a 6-year PFS of 76.8% and 62%, respectively, which were lower than RT alone (PFS = 89.6%) or ABVD+RT (PFS = 94.3%) (p < 0.001). Of the cohort, there were 127 treatment failures (16.3%), of which 25 patients (3.2%) had transformations. On univariable and multivariable cox regression adjusted for LP-IPS, treatment with ABVD alone had an inferior PFS compared to all management approaches with RT (hazard ratio = 2.08, p < 0.001) with no significant OS difference on univariable analysis. Six of the 12 lymphoma-specific deaths involved transformation events. There were local relapses in 15/25 observation alone and 5/12 ABVD compared to none in the RT alone or RT-containing regimens (p < 0.001). Conclusions: PFS for patients with complete excision who received RT was superior compared to observation alone, plus reduction of local recurrences. Creation of a patient decision aid to guide patients and caregivers with individual risk/benefit assessment between these 2 viable options is warranted. For patients with stage IA disease without complete excision, both ABVD and rituximab alone have inferior PFS compared to RT or combined modality therapy, highlighting the importance to consider inclusion of RT in localized, lower risk RT sites for stage IA NLPHL management. These findings provide data to design a prospective trial to establish data-driven standards of care for adequate treatment of stage IA NLPHL. Research funding declaration: Stanford University, Wilmot Cancer Institute, Lymphoma Research Foundation Keywords: Hodgkin lymphoma; Hodgkin lymphoma (Pediatric, Adolescent, and Young Adult) Potential sources of conflict of interest: K. J. Savage Consultant or advisory role: Celgene, Seagen Honoraria: BMS, Merck, Gilead, Astra Zeneca, Janssen, Abbvie Other remuneration: Steering committee: Beigene; DSMC: Regeneron R. Steiner Other remuneration: Research funding from Seagen, BMS, GSK and Rafael Pharmaceuticals, NCI A. Prica Honoraria: Astra-Zeneca, Abbvie, Kite Gilead P. McKay Other remuneration: Honoraria/consulting: Abbvie, AstraZeneca, Beigene, Celgene/BMS, Epizyme/Ipsen, Gilead/Kite, Incyte, Janssen, Roche, Sobi, Takeda W. Osborne Other remuneration: Roche B. S. Hoppe Consultant or advisory role: Merck D. Talaulikar Honoraria: Roche, Janssen, Beigene, Amgen, EUSA, CSL, and Antengene Other remuneration: Research funding from Roche, Takeda and Jansen E. Hawkes Consultant or advisory role: Roche, Merck Sharpe & Dohme, Astra Zeneca, Gilead, Antigene, Novartis, Regeneron, Janssen, Specialised Therapeutics Educational grants: Astra Zeneca Other remuneration: Research funding (paid to institution): Roche, Bristol Myers Squibb, Merck KgA, Astra Zeneca and Merck. A. Barraclough Honoraria: Beigene, Gilead, Roche and Novartis S. Opat Other remuneration: advisory role and received honoraria from Abbvie, Antengene, AstraZeneca, Beigene, CSL Behring, Gilead, Janssen, Merck, Roche and Takeda; institution has received research funding from Abbvie, AstraZeneca, Beigene, Gilead, Janssen, Pharmacyclics, Roche and Takeda.​ C. Y. Cheah Other remuneration: consulting/advisory/honoraria—Roche, Janssen, Gilead, AstraZenecca, Lilly, Beigene, Menarini, Dizal, Abbvie, Genmab. BMS; research funding—BMS, Roche, Abbvie; MSD, Lilly