A new combination therapy could soon reshape care for younger patients with hard-to-treat Hodgkin lymphoma in Europe. The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use has recommended the approval of Opdivo (nivolumab, Bristol Myers Squibb Pharma EEIG) in combination with brentuximab vedotin for children aged 5 years or older, adolescents, and adults up to 30 years of age with relapsed or refractory classical Hodgkin lymphoma (cHL) after one prior line of therapy. 

The decision, which would expand treatment options for children, adolescents, and young adults, now awaits a final ruling by the European Commission.

The new indication would add to Opdivo’s extensive list of existing European Union approvals, which include melanoma, non-small cell lung cancer, malignant pleural mesothelioma, renal cell carcinoma, squamous cell cancer of the head and neck, urothelial carcinoma, colorectal cancer, esophageal squamous cell carcinoma, gastric cancer, and hepatocellular carcinoma.

How the PD-1 Inhibitor Works 

Nivolumab is a PD-1 checkpoint inhibitor that showed efficacy in relapsed or refractory cHL after autologous hematopoietic cell transplantation. Genetic changes causing overexpression of PD-1 ligands are nearly universal in cHL, with changes at 9p24.1 leading to overexpression of PD-L1 and PD-L2 on tumor cell surfaces. The drug blocks signaling through the PD-1 pathway, releasing inhibition of T cells and enhancing antitumor immune responses.

What Evidence Shows 

Although the EMA’s positive opinion does not explicitly cite a single pivotal phase 3 trial, supportive evidence comes from the phase 2 CheckMate 744 study in children, adolescents and young adults aged 5-30 years with relapsed or refractory cHL. 

In this risk-adapted study, induction with nivolumab and brentuximab vedotin achieved a complete metabolic response rate of about 59%, and when followed by additional therapy before consolidation, this rate reached 94%. The 1-year progression-free survival rate was about 91%, with an acceptable safety profile. 

Although the regimen included response-adapted intensification (eg, brentuximab plus bendamustine for nonresponders), the high response and survival rates provide a clinical rationale for regulatory evaluation of the combination in this younger population.

Detailed recommendations for using this product will be described in the updated Summary of Product Characteristics, which will be published on the EMA’s website in all official European Union languages after the European Commission grants a decision on this marketing authorization change.