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
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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