206 - Safety of Maintenance Pembrolizumab (Pembro) and Concurrent Radiotherapy (RT) in Pediatric Participants with Classic Hodgkin Lymphoma (cHL) and Slow Early Response (SER) to Front-Line Chemotherapy (Chemo): Post Hoc Analysis of the KEYNOTE-667 Study
Presenter(s)
B. S. Hoppe1, L. Roth2, K. M. Kelly3, D. Hodgson4, S. Castellino5, F. Eberle6, D. Vordermark7, A. Beishuizen8, L. Valero9, S. Daw10, K. A. Lopez11, M. Castellanos12, L. Vinti13, J. Shen14, P. Pillai14, R. Yusuf14, and C. Mauz-Korholz15,16; 1Mayo Clinic, Department of Radiation Oncology, Jacksonville, FL, 2Weill Cornell Medicine, New York, NY, 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, 4Princess Margaret Cancer Centre, Toronto, ON, Canada, 5Emory University, Children’s Healthcare of Atlanta, Atlanta, GA, 6University Clinic of Gießen and Marburg, Marburg Ion Beam Treatment Center, Marburg, Germany, 7University of Halle, Halle, Germany, 8Princess Máxima Centre, Utrecht, Netherlands, 9Hospital Universitari Vall d’Hebron, Barcelona, Spain, 10University College London Hospitals NHS Foundation Trust, London, Spain, 11Oncomedica, Guatemala City, Guatemala, 12Unidad Nacional de Oncología Pediátrica, Guatemala City, Guatemala, 13IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, 14Merck & Co., Inc., Rahway, NJ, 15Medical Faculty of the Martin-Luther-University of Halle-Wittenberg, Halle, Germany, 16Justus-Liebig University of Giessen, Giessen, Germany
Purpose/Objective(s): The safety of concurrent pembro and RT in children and young adults with cHL is unkown. In the phase 2 KEYNOTE-667 study, consolidation with pembro plus chemo with or without RT and maintenance pembro had promising efficacy and manageable safety in participants (pts) with low-risk (LR) and high-risk (HR) cHL and SER to front-line chemo. We present a post hoc analysis of the safety of maintenance pembro with or without RT.
Materials/Methods: Pts aged 3-25 y with newly diagnosed stage IA, IB, or IIA cHL without bulky disease (LR) or stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL (HR) received 2 cycles of induction chemo then underwent early response assessment by PET and CT/MRI. Pts with SER (Deauville score [DS] 4 or 5) received consolidation with pembro 2 mg/kg up to 200 mg (aged 3-17 y) or 200 mg (aged 18-25 y) IV Q3W plus 2 cycles of AVD (LR) or 4 cycles of COPDAC-28 (HR). Pts then underwent late response assessment (LRA). Pts with LR cHL and SER with PET-negative disease (DS 1-3) at LRA received involved-site RT (ISRT) to 21.6 Gy; pts with PET-positive disease (DS 4 or 5) at LRA received PET-directed residual site RT boost to 30.6-36 Gy. Pts with HR cHL and SER who had PET-positive disease (DS 4 or 5) at LRA received ISRT to 28.8 Gy to late PET-positive residua; pts with PET-negative disease (DS 1-3) received no RT. All pts received maintenance pembro Q3W for a total of 17 doses. Incidence of AEs was evaluated for 6 mo after the start of RT (pts who received RT and maintenance pembro) or the start of maintenance pembro (pts who received no RT).
Results: 78 pts with LR and 246 with HR cHL received induction. 10 of 78 pts with LR cHL had SER and received consolidation with pembro plus AVD followed by RT (21.6 Gy, n = 6; 30.6-36 Gy, n = 4) and maintenance pembro. 84 of 246 pts with HR cHL had SER and received consolidation with pembro plus COPDAC-28 and maintenance pembro; 17 received RT =28.8 Gy and 67 received no RT. Median (range) time from enrollment to database cutoff (Oct 1, 2025) was 39.0 mo (24.6-63.9) in pts with LR cHL with SER, and 43.4 mo (24.7-67.5) in pts with HR cHL with SER. Of 27 pts who received RT (10 LR SER, 17 HR SER), 20 (74%) had any-cause AEs (grade =3, n = 12 [44%]). Pulmonary AEs occurred in 6 of 27 pts (22%) who received RT (all grade 1 or 2) and 11 of 67 pts (16%) who received no RT (grade =3 pneumonitis, n = 1 [1%]); the most common pulmonary AE in both groups was cough, occurring in 5 of 27 (19%) and 7 of 67 pts (10%), respectively (all grade 1 or 2). Of 67 pts who did not receive RT in the HR SER population, 43 (64%) had any-cause AEs (grade =3, n = 6 [9%]).
Conclusion: In this post hoc analysis, concurrent maintenance pembro and RT in children and young adults with cHL and SER to front-line chemo resulted in a low incidence of pulmonary AEs. Further studies are warranted to confirm these findings. (NCT03407144)