Background: ECHELON-1 is a phase 3 study of BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) vs ABVD as frontline therapy in untreated advanced HL (NCT01712490). G-CSF primary prophylaxis (G-PP) was administered at the investigators’ discretion, and during the study was formally recommended by an independent data monitoring committee (IDMC) for patients (pts) receiving A+AVD. For pts receiving A+AVD, G-PP was associated with fewer infections and ≥ Grade 3 AEs, including neutropenia (70% without vs 29% with G-PP) and febrile neutropenia (21% vs 11%). Methods: Exploratory analyses assessing outcomes and exposure in pts who received G-PP on the A+AVD arm compared with those who did not were conducted. G-PP was defined as use of G-CSF by Day 5 of treatment (tx); non-G-PP pts included pts who received G-CSF secondary prophylaxis. Results: 1334 pts with advanced HL were randomized 1:1 to receive A+AVD or ABVD. In 662 pts treated with A+AVD, G-PP was given to 42 of 499 pts who started tx prior to, and 41 of 163 pts who started tx after the IDMC recommendation. Across tx arms, baseline characteristics were similar between the subgroups. G-PP, compared with no G-PP, was associated with a lower rate of BV dose delays (35% vs 49%) and dose reductions (20% vs 26%), and decreased hospitalization rates (pts with at least 1 hospitalization 29% vs 38%). Of the 7 neutropenia-associated deaths during A+AVD tx, none occurred in pts who received G-CSF prior to the onset of neutropenia. A+AVD with G-PP was associated with a decreased risk of a modified progression free survival event (mPFS; Connors, 2018) by 25% compared to A+AVD without G-PP and by 42% compared to ABVD. Clinical trial information: NCT01712490Conclusions: Concomitant administration of G-PP with A+AVD in pts with advanced HL reduced AEs and frequency of tx delays. Though the sample size is small, G-PP with A+AVD may be associated with improved efficacy and a decrease in early, neutropenia-associated deaths; a prospective clinical trial to further assess the safety and efficacy in pts receiving G-PP with A+AVD is planned.