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462 Pembrolizumab in Children, Adolescents, and Young Adults with Low-Risk Classic Hodgkin Lymphoma (cHL) and Slow Early Response to Front-Line Chemotherapy: Updated Results from the Phase 2 Keynote-667 Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas: Clinical and Epidemiological: Potentially Practice-Changing Trials in Hodgkin Lymphoma
Hematology Disease Topics & Pathways:
Research, Clinical trials, Hodgkin lymphoma, Lymphomas, Clinical Research, Chemotherapy, Checkpoint Inhibitor, Pediatric, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Non-Biological therapies, Young adult , Radiation Therapy, Study Population, Human
Sunday, December 8, 2024: 10:45 AM

Lisa Giulino Roth, MD1, Mario Melgar Toledo2*, Frank G. Keller3*, Bradford Hoppe4*, Christopher J. Forlenza, MD5, Sharon M. Castellino, MD, MSc3, Maitane Andión Catalan6*, Julie Krystal7*, Adam Lamble, MD8, Flavio Luisi9*, Fabio Molina Morales10*, Aarati V. Rao11, Stacy Cooper12, Oscar Gonzalez Llano13*, Luis Juarez Villegas14*, Christine Mauz-Koerholz, MD15,16, Juan Shen17*, Pallavi Pillai, MD17, Rushdia Yusuf17 and Kara M. Kelly, MD18

1Weill Cornell Medicine, New York, NY
2Unidad Nacional de Oncología Pediátrica, Guatemala City, Guatemala
3Children's Healthcare of Atlanta at Egleston, Atlanta, GA
4Mayo Clinic, Jacksonville, FL
5Memorial Sloan Kettering Cancer Center, New York, NY
6Hospital Infantil Universitario Niño Jesús, Madrid, Spain
7Cohen Children's Medical Center of New York, Queens, NY
8Hematology-Oncology, Seattle Children's Hospital, Seattle, WA
9Instituto de Oncología Pediátrica—GRAACC—UNIFESP, São Paulo, Brazil
10Oncomédica S.A.S, Monteria, Colombia
11Kaiser Permanente Roseville Medical Center, Roseville, CA
12Johns Hopkins University, Baltimore, MD
13Hospital Universitario "Dr. José Eleuterio Gonzalez", Monterrey, Mexico
14Hospital Infantil de México Federico Gómez, Mexico City, Mexico
15Medical Faculty of the Martin-Luther-University of Halle-Wittenberg, Halle, Germany
16Justus-Liebig University of Giessen, Giessen, Germany
17Merck & Co., Inc., Rahway, NJ
18Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY

Background: Cure rates for children, adolescents, and young adults with cHL are high, but patients with a slow early response (SER) to front-line chemotherapy are at an increased risk of relapse compared with patients who have a rapid early response (RER). To avoid long-term toxicity while optimizing outcomes, treatment for pediatric cHL is now shifting to a response-adapted approach. KEYNOTE-667 (NCT03407144) is an open-label phase 2 study designed to evaluate the efficacy and safety of pembrolizumab plus chemotherapy consolidation with or without radiotherapy (RT) followed by pembrolizumab maintenance in patients with cHL and SER to front-line chemotherapy. The study includes 2 groups of patients: those with low-risk cHL (stage IA, IB, and IIA without bulky disease) and those with high-risk cHL (stage IIEB-IVB cHL). Prior analysis of the low-risk group showed that consolidation with pembrolizumab plus doxorubicin, vinblastine, and dacarbazine (AVD) and RT followed by maintenance pembrolizumab had manageable safety and promising antitumor activity in patients with low-risk cHL and SER to front-line doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). We present updated results for patients with low-risk cHL and SER to ABVD.

Methods: Patients eligible for the low-risk group were aged 3-25 years and had newly diagnosed stage IA, IB, or IIA cHL without bulky disease, measurable disease, and a Lansky Play-Performance Scale score of ≥50 (aged <16 years) or a Karnofsky Performance Status score of ≥50 (aged ≥16 years). All patients in the low-risk group received 2 cycles of ABVD followed by early response assessment (PET and CT/MRI). Patients with a RER (ie, Deauville score [DS] 1-3) received nonstudy therapy. Patients with SER (ie, DS 4 or 5) received consolidation with pembrolizumab 2 mg/kg up to 200 mg (aged 3-17 years) or 200 mg (aged 18-25 years) IV Q3W plus 2 cycles of AVD. Patients then underwent late response assessment (LRA; PET and MRI/CT). All patients with SER received involved-site RT: 21.6 Gy for complete PET response (ie, DS 1-3) or 30.6-36 Gy for partial PET response (ie, DS 4 or 5). All patients received maintenance pembrolizumab for up to 17 cycles. The primary end point was objective response rate (ORR) by blinded independent central review (BICR) per Cheson 2007 IWG criteria. Secondary end points included PET negativity after consolidation and safety.

Results: 78 patients with low-risk cHL received front-line ABVD. As of the data cutoff date (February 29, 2024), 10 of 78 patients had SER to ABVD and received consolidation with pembrolizumab plus AVD; 4 had completed consolidation and maintenance, 1 was continuing to receive treatment, and 5 had discontinued because of complete response (CR). Median time from allocation to data cutoff was 19.9 months (range, 5.6-44.8). Patients had received a median of 11.5 doses of pembrolizumab (range, 5-17) and the median time on pembro was 7.4 months (range, 3.5-11.3). The median age of patients was 16 years (range, 7-20), 6 (60%) were male, and 8 (80%) had Ann Arbor stage II disease. Of 10 patients who received consolidation, all (100%) had an LRA. The ORR was 100% (95% CI, 69-100; 9 CR and 1 partial response). Six patients (60%) were PET negative by BICR. Seven patients (70%) were PET negative by investigator review, all of whom received a reduced dose of RT. During consolidation, treatment-related adverse events (AEs) were reported in 8 patients (80%); grade 3 or 4 treatment-related AEs occurred in 4 patients (40%). No patients discontinued or died due to treatment-related AEs. Seven patients (67%) had pembrolizumab-related AEs, 3 of whom (30%) had a grade 3 event (vomiting, lymphocyte count decreased, white blood cell count decreased). Immune-mediated AEs occurred in 3 patients (30%; all grade 1 or 2 hypothyroidism).

Conclusion: After additional follow-up, consolidation with pembrolizumab plus AVD and RT followed by pembrolizumab maintenance continued to demonstrate promising activity and manageable safety in patients with low-risk cHL and SER to ABVD. Of patients with a LRA, 60% were PET negative by BICR; 70% of patients were PET negative by investigator review and received a reduced dose of RT. These results support further evaluation of pembrolizumab plus AVD consolidation as a treatment option for patients with low-risk CHL and SER to front-line ABVD.

Disclosures: Roth: Merck: Consultancy; Roche: Consultancy. Melgar Toledo: Merck: Consultancy; Merck, Pfizer: Research Funding. Keller: Merck & Co., Inc.: Honoraria. Hoppe: Merck: Research Funding. Forlenza: Bristol Myers Squibb: Consultancy. Castellino: BMS: Consultancy, Honoraria; SeaGen Inc.: Consultancy, Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees, Research Funding; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees. Krystal: DayOne Bio: Consultancy. Luisi: Janssen, Libbs, MSD: Speakers Bureau; MSD: Other: Travel, accommodations, expenses. Cooper: Novartis: Honoraria; Jazz Pharmaceuticals: Consultancy. Mauz-Koerholz: Merck: Other: Research funding to my institution. Shen: Merck & Co., Inc.: Current Employment, Current holder of stock options in a privately-held company. Pillai: Merck & Co., Inc.: Current Employment, Current holder of stock options in a privately-held company. Yusuf: Merck & Co., Inc., Rahway, NJ, USA: Current Employment. Kelly: Seagen: Membership on an entity's Board of Directors or advisory committees.

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