As reported in JAMA Oncology by Daw et al, findings in a cohort of the phase II CheckMate 744 trial indicated good outcomes with a response-adapted, transplantation-free treatment approach in children and adolescents and young adults (AYAs) with low-risk relapsed classical Hodgkin lymphoma (HL).
Study Details
In the cohort (R1), 28 patients (aged 5–30 years) were enrolled from sites in the United States, Canada, and Europe between September 2017 and December 2020. Patients received four cycles of nivolumab plus brentuximab vedotin (BV) induction. Those with complete metabolic response received an additional two cycles of nivolumab plus BV, whereas those with suboptimal response received two cycles of BV plus bendamustine intensification. Patients with complete metabolic response after induction or intensification received involved-site radiotherapy (ISRT; 30.0–30.6 Gy) consolidation. In 21-day cycles, nivolumab at 3 mg/kg was given on day 8 of cycle 1 and day 1 of each subsequent cycle for up to six cycles; BV at 1.8 mg/kg was given on day 1 of each cycle; and bendamustine at 90 mg/m2 was given on days 1 and 2 of each cycle. The main outcome measures were complete metabolic response rate at any time before ISRT and 3-year event-free survival rate on blinded independent central review.
Key Findings
Median follow-up was 31.9 months (range = 2.2–55.3 months). Among the 28 patients, complete metabolic response was achieved at any time before ISRT in 26 (93%, 90% confidence interval [CI] = 79.2%–98.7%), with an objective response rate of 100%. A total of 23 patients (82%) achieved complete metabolic response after four cycles of nivolumab plus BV, with an objective response rate of 96.4%. Kaplan-Meier estimates of event-free survival and progression-free survival at 3 years were 87% (90% CI = 69.5%–94.7%) and 95% (90% CI = 76.7%–99.0%), respectively.
The most common treatment-related adverse events of any grade during induction were increased alanine aminotransferase (21%), headache (18%), and infusion-related reaction (18%). Grade 3 or 4 treatment-related adverse events occurred in seven patients (25%), including immune-mediated adverse events in six patients. Serious treatment-related adverse events were reported in 18% of patients. No treatment-related deaths were observed.
The investigators concluded: “This nonrandomized clinical trial found that for children, adolescents, and young adults with low-risk, relapsed classical HL, a transplant-free, risk-adapted, response-based approach with nivolumab plus BV and ISRT offered high [complete metabolic response] rates and high 3-year [event-free survival] rate, with a safety profile consistent with that of each agent used.”
Stephen Daw, MD, of the Paediatric Division, University College Hospital, London, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb through the joint financial support of Bristol Myers Squibb and Seagen. For full disclosures of all study authors, visit JAMA Oncology.
