{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:08:20Z","timestamp":1788174500274,"version":"build-2803163510"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"Importance<\/jats:title>Retrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.0 to 30.6 Gy).<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>CheckMate 744 (R1 cohort) was a phase 2, nonrandomized, single-arm study enrolling children, adolescents, and young adults aged 5 to 30 years with low-risk cHL between September 25, 2017, and December 16, 2020, across the US, Canada, and Europe. Data were analyzed from September 2017 to November 2022.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Patients received 4 cycles of nivolumab plus BV induction; patients with complete metabolic response (CMR) received an additional 2 cycles of nivolumab plus BV while patients with suboptimal response received 2 cycles of BV plus bendamustine intensification. Patients with CMR after induction or intensification received ISRT consolidation.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Prespecified coprimary end points were CMR rate (Lugano 2014 classification) any time before ISRT and 3-year event-free survival (EFS) rate, per blinded independent central review (BICR).<\/jats:p><\/jats:sec>Results<\/jats:title>Of 28 included patients treated in the low-risk cohort, 18 (64%) were female, and the median (range) age was 17 (6-27) years. At a median (range) follow-up of 31.9 (2.2-55.3) months, CMR per BICR any time before ISRT was 93% (26 of 28; 90% CI, 79.2-98.7; objective response rate [ORR], 100%), and 23 of 28 (82%) achieved CMR per BICR after 4 cycles of nivolumab plus BV (ORR, 96.4%). Kaplan-Meier estimates of EFS and progression-free survival rates at 3 years were 87% (3 of 18; 90% CI, 69.5-94.7) and 95% (1 of 18; 90% CI, 76.7-99.0), respectively. During induction, 22 patients (79%) had treatment-related adverse events, including 7 with grade 3 or 4 adverse events, 2 with anemia, 1 with neutropenia, and 6 with immune-mediated adverse events. Serious adverse events leading to discontinuation occurred in 2 patients.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>This nonrandomized clinical trial found that for children, adolescents, and young adults with low-risk, relapsed cHL, a transplant-free, risk-adapted, response-based approach with nivolumab plus BV and ISRT offered high CMR rates and high 3-year EFS rate, with a safety profile consistent with that of each agent used.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT02927769<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2024.5627","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T16:00:59Z","timestamp":1735833659000},"page":"249","source":"Crossref","is-referenced-by-count":21,"title":["Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young 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