Most children, adolescents, and young adults with classic Hodgkin lymphoma (cHL) can be cured with first-line treatment; however, patients with relapsed or refractory disease are at risk for experiencing worse outcomes. In the multicenter, phase 2 CheckMate 744 trial, MCW investigators tested a new salvage therapy approach that incorporated targeted therapy, immunotherapy, and chemotherapy. Their results, published in Blood, showed that this strategy may be safer and more effective than the standard of care for treating pediatric patients with relapsed cHL. “The risk-stratified, response-adapted strategy used within the study helped patients achieve the highest complete metabolic response (CMR) rates of any pediatric salvage trial to date,” said Paul Harker-Murray, MD, PhD, Associate Professor, Pediatric Oncology and first author of the study. “Our therapy was extremely well tolerated with minimal side effects compared to conventional retrieval trials. We hope that reducing toxicity will improve patient outcomes and lead to higher cure rates with fewer long term side effects.”
During the trial, 44 patients aged 5 to 30 received four induction cycles of the checkpoint inhibitor, nivolumab, and brentuximab vedotin (BV), followed by targeted radiotherapy if they achieved CMR. Those who did not achieve CMR after the initial treatment received two additional cycles of BV and bendamustine (chemotherapy) prior to radiotherapy. The results showed that the CMR rate after nivolumab and BV induction was 59%, and increased to 94% with BV and bendamustine intensification. Dr. Harker-Murray noted that most patients did not require chemotherapy, which may help to minimize the risk of acute and chronic toxicities.
The current standard of care for treating pediatric patients with cHL is providing therapy to achieve remission and then consolidating with chemotherapy and autologous hematopoietic cell transplantation (AHCT). However, a growing body of research shows that many patients with low-risk relapsed cHL can be cured without these secondary treatments. Findings from CheckMate 744 help to further define a population of patients with low-risk relapsed cHL who do not require transplantation to be cured. “This has the potential to change the standard of care and inspire future clinical trials,” said Dr. Harker-Murray.
This research will serve as the inspiration for a larger combined pediatric and adult trial that randomizes patients with relapsed disease to either receive or not receive AHCT as part of their therapy. Dr. Harker-Murray and the study team hope the next-generation trial will continue to redefine treatment standards for cHL and improve outcomes for both pediatric and adult patients with relapsed disease.