Background: NLPHL is a rare subtype of Hodgkin lymphoma (HL) accounting for 5% of cases. It is rarely studied in prospective clinical trials and treatment is controversial. Methods: In the Canadian Cancer Trials Group HD.6 phase 3 trial, individuals with newly diagnosed non-bulky stage IA or IIA HL were randomly assigned to treatment with ABVD chemotherapy (CT) alone, or to radiation based (CMT/RT) therapy [Meyer NEJM 2012]. From this we identified all patients with NLPHL. A classical Hodgkin lymphoma (cHL) comparison cohort was constructed using propensity score matching 3:1 for age, sex, stage, treatment arm and number of nodal sites. Event free survival (EFS), overall survival (OS) and freedom from disease progression (FFP) were as defined in the original trial. The NLPHL cohort was analyzed according to treatment arm and compared with the cHL cohort using log-rank statistics. Secondary endpoints included toxicity and second malignancies. Results: Of 405 individuals enrolled in HD.6, 29 (7.2%) had NLPHL. Of these, median age at diagnosis was 42 yrs, 24 (83%) were male and 15 were assigned to RT. Median follow up was 120 months. For patients with NLPHL, 12-yr EFS for CMT/RT vs CT was 58% vs. 85% (HR 0.46, 95% CI 0.09-2.37) and FFP was 70% vs 85% (HR 0.72, 95% CI 0.12-4.33), respectively. There was one death in the CMT/RT arm; OS analysis by treatment arm was not conducted due to insufficient events. Eighty-seven pts were identified for the matched cHL cohort. 12-yr OS in the NLPHL and cHL groups was 95% and 87% (HR 3.43, 95% CI 0.44-26.5), EFS 70% and 81% (HR 0.73, 95% CI 0.30-1.76), FFP 78% and 90% (HR 0.51, 95% CI 0.17-1.57). Over the entire course of follow-up, there was 1 (3%) death in the NLPHL group due to unknown cause and 12 (14%) deaths in the cHL group – 3 treatment-related toxicity, 6 secondary malignancy, 3 other causes. Conclusions: We present the only prospective assessment of early-stage NLPHL treated with ABVD alone. Acknowledging limitations including small sample size, outcomes of pts with NLPHL appear very good when treated with ABVD chemotherapy alone. Clinical trial information: NCT 00002561.