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Clinical Trial
. 2025 Mar 1;11(3):249-257.
doi: 10.1001/jamaoncol.2024.5627.

Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial

Stephen Daw  1 , Peter D Cole  2 , Bradford S Hoppe  3 , David Hodgson  4 , Auke Beishuizen  5 , Nathalie Garnier  6 , Salvatore Buffardi  7 , Maurizio Mascarin  8 , Andrej Lissat  9 , Christine Mauz-Körholz  10 , Jennifer Krajewski  11 , Alev Akyol  11 , Russell Crowe  12 , Bailey Anderson  11 , Yan Xu  13 , Richard A Drachtman  2 , Kara M Kelly  14 , Thierry Leblanc  15 , Paul Harker-Murray  16
Affiliations
Clinical Trial

Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial

Stephen Daw et al. JAMA Oncol. .

Abstract

Importance: 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).

Objective: 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).

Design, setting, and participants: 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.

Exposures: 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.

Main outcomes and measures: 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).

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT02927769.

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Conflict of interest statement

Conflict of Interest Disclosures: Mr Hodgson has received grants from the Canadian Cancer Society and has served as the Medical Director for the Pediatric Oncology Group of Ontario. Dr Lissat has received grants from the Deutsche José Carreras Stiftung; has held a leadership or fiduciary role for AIEOP BFM, INFORM, IntReALL, and ITCC Hema; and holds stock in AbbVie, Bristol Myers Squibb, Gilead, Pfizer, and Roche. Dr Mauz-Körholz has received grants paid to her institution from Merck; has participated in data safety monitoring or advisory boards for Bristol Myers Squibb and Merck; and has held a leadership or fiduciary role for EuroNet-PHL. Dr Krajewski has received travel support from and holds stock in Bristol Myers Squibb. Mr Crowe holds stock in Bristol Myers Squibb. Ms Xu has received consulting fees from Bristol Myers Squibb. Dr Kelly has received grants paid to her institution from Merck and has held a leadership or fiduciary role for the Lymphoma Research Foundation and Seagen. Dr Leblanc has received honoraria from Novartis and Takeda and has participated in data safety monitoring or advisory boards for Bristol Myers Squibb. No other disclosures were reported.

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References

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