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1700 Pembrolizumab (pembro) in Children and Young Adults with Low-Risk Classical Hodgkin Lymphoma (cHL) with Slow Early Response (SER) to Front-Line Chemotherapy (chemo): Early Results from the Phase 2 Keynote-667 Study

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphomas and T/NK Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
clinical trials, Hodgkin lymphoma, Checkpoint Inhibitor, pediatric, young adult
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Lisa Giulino Roth, MD1, Frank Keller, MD2*, Mario Melgar Toledo3*, Sharon M. Castellino, MD, MSc2, Christopher J. Forlenza, MD4, Maitane Andión Catalan5*, Julie Krystal, MD6*, Adam Lamble, MD7*, Aarati V. Rao, MD, MBBS8, Fabio Molina Morales9*, Stacy Cooper, MD10, Flavio Luisi11*, Oscar Gonzalez Llano12*, Karla Alejandra Lopez13*, Christine Mauz-Koerholz, MD14,15, Bradford Hoppe, MD, MPH16*, Juan Shen17*, Pallavi Pillai, MD17, Patricia Marinello, PharmD17 and Kara M. Kelly, MD18

1Weill Cornell Medicine, New York
2Children's Healthcare of Atlanta at Egleston, Atlanta, GA
3Unidad Nacional de Oncologia Pediatrica, Guatemala City, Guatemala
4Memorial Sloan Kettering Cancer Center, New York, NY
5Hospital Infantil Universitario Nino Jesus, Madrid, Spain
6Cohen Children's Medical Center of New York, Queens, NY
7Seattle Childrens Hospital, Seattle, WA
8Kaiser Permanente Roseville Medical Center, Roseville, CA
9Oncomédica S.A.S, Monteria, Colombia
10Johns Hopkins University, Baltimore, MD
11Instituto de Oncologia Pediatrica - GRAACC – Unifesp, Sao Paulo, Brazil
12Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Mexico, Monterrey, Mexico
13Oncomedica, Guatemala City, Guatemala
14Justus-Liebig University of Giessen, Giessen, Germany
15Medical Faculty of the Martin-Luther-University of Halle-Wittenberg, Halle, Germany
16Mayo Clinic, Jacksonville, FL
17Merck & Co., Inc., Rahway, NJ
18Roswell Park Comprehensive Cancer Center, Buffalo, NY

Background: Pediatric patients (pts) with low-risk cHL achieve high cure rates with standard chemo. However, those with a SER to front-line chemo are at higher risk of relapse than pts with a rapid early response (RER). Current treatment options are also associated with long-term toxicities such as secondary malignancies, cardiovascular disease, and pulmonary and gonadal toxicity. Novel treatment approaches are needed to optimize outcomes while minimizing long-term toxicity. KEYNOTE-667 (NCT03407144) is an open-label, phase 2 study that included an analysis of safety and efficacy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) induction in pediatric pts with low-risk cHL followed by consolidation with pembro plus AVD and involved-site radiotherapy (ISRT) and pembro maintenance in those with SER to front-line ABVD. We present an interim analysis of pts with low-risk cHL enrolled in this trial.

Methods: Eligible pts were 3-25 y old and had newly diagnosed stage IA, IB, or IIA cHL without bulky disease, measurable disease per investigator assessment, and a Lansky Play-Performance Scale ≥50 (aged <16 y) or a Karnofsky score of ≥50 (aged ≥16 y). Pts initially received 2 cycles of induction with ABVD. Response was then assessed by PET/MRI/CT (early response assessment). Pts with RER received nonstudy therapy per treating physician. Pts with SER (Deauville score [DS], 4 or 5) received consolidation with pembro 2 mg/kg up to 200 mg IV Q3W (3-17 y) or 200 mg IV Q3W (18-25 y) in combination with 2 cycles of AVD followed by a late response assessment (LRA) with PET/MRI/CT. All pts with a SER then received ISRT (21.6 Gy for pts with a complete PET response [DS, 1-3]; 30.6-36 Gy for pts with a partial PET response [DS, 4 or 5]) plus maintenance pembro Q3W for up to 17 cycles. Primary end point was ORR by blinded independent central review (BICR) per Cheson 2007 IWG criteria in pts with SER determined at any time after starting pembro and before start of new anticancer therapy. Secondary end points included rate of PET negativity after consolidation, EFS, OS, and safety.

Results: 73 pts with low-risk cHL were enrolled, 9 of whom had SER to ABVD induction. 64 pts had a RER and received nonstudy treatment. At data cutoff (March 1, 2023), 2 of 9 pts (22%) with SER had completed consolidation and maintenance therapy, 5 (56%) were ongoing, and 2 (22%) had discontinued, both because of complete response. Median time from enrollment to data cutoff was 8.7 mo (range, 2.2-32.9). Median age was 16 y (range, 7-20), 5 pts (56%) were male, 2 (22%) had Ann Arbor stage I disease, and 7 (78%) had Ann Arbor stage II disease. Pts with SER had received a median of 8 doses of pembro (range, 1-17); median time on pembro was 4.8 mo (range, <0.1-11.3). Of 9 pts who received consolidation therapy with pembro plus AVD, 6 (67%) had a LRA (3 are still in consolidation and have not reached the LRA timepoint), of whom 3 (50%) were PET negative by BICR (2 [33%] were PET negative by investigator review). Of 73 pts who received ABVD induction, 66 (90%) had an AE regardless of causality. 33 pts (45%) experienced grade 3/4 AEs, most commonly (≥10%) neutrophil count decreased (n = 19; 26%) and neutropenia (n = 9; 12.3%). One pt experienced grade 4 febrile neutropenia. Twelve pts (16%) had serious AEs. No pts discontinued treatment or died because of AEs. Treatment-related AEs due to ABVD induction occurred in 59 pts (81%), with grade 3/4 events in 31 (42%). Of the 9 pts with SER to ABVD induction who received consolidation and maintenance therapy, 7 (78%) experienced an AE regardless of causality. Two pts (22%) had grade 3/4 AEs. No serious AEs were reported during consolidation and maintenance therapy, and no pts discontinued treatment or died because of AEs. Treatment-related AEs occurred in 6 pts (67%) who received consolidation and maintenance therapy; with grade 3/4 events in 2 pts (22%). Six pts (67%) experienced AEs related to pembro; most commonly (≥3 pts) anemia, nausea, vomiting (n = 3 each [33%]). Two pts experienced grade 3/4 AEs related to pembro (vomiting, white blood cell count decreased). One pt (11%) experienced an immune-mediated AE (grade 2 hyperthyroidism).

Conclusion: Early results from the low-risk cHL cohort of KEYNOTE-667 suggest that induction therapy with ABVD and consolidation with pembro plus AVD had a manageable safety profile. Among the relatively small number of pts with a SER to ABVD, 50% with a LRA had a PET-negative response by BICR and received a reduced dose of RT.

Disclosures: Roth: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees. Keller: Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Scientific advisory council. Melgar Toledo: MSD: Other: Travel/Accommodations/Expenses, Research Funding, Speakers Bureau; Pfizer: Consultancy, Other: Expert testimony, Research Funding. Castellino: SeaGen Inc.: Other: Scientific Advisory Committee - No honoraria, Research Funding; Bristol Meyers Squibb: Honoraria, Other: Scientific Advisory Committee. Rao: TPMG: Chief of Pediatric Surgery: Kaiser Roseville; COG PI for Kaiser Oakland: Other: Leadership Role. Cooper: Pfizer: Consultancy; Jazz: Consultancy. Luisi: MSD: Other: Travel/Accommodations/Expenses, Speakers Bureau; Takeda: Speakers Bureau; Sanofi: Speakers Bureau. Mauz-Koerholz: Merck/MSD: Research Funding. Hoppe: Merck SAC for AHOD1822/KN667 low risk: Consultancy. Shen: Merck: Current Employment, Current equity holder in publicly-traded company. Pillai: Merck & Co., Inc.: Current Employment, Current equity holder in publicly-traded company. Marinello: Merck & Co., Inc.: Current Employment, Current equity holder in publicly-traded company. Kelly: Seagen AYA Lymphoma Advisory Board (nonpaid): Other: Non-remunerated activity.

*signifies non-member of ASH