Dacarbazine

The EC approval is based on the Phase II CheckMate-744 trial in classical Hodgkin Lymphoma patients. Credit: Saiful52 / Shutterstock.com. Bristol Myers Squibb’s (BMS) Opdivo (nivolumab) has received approvals for two new indications in classical Hodgkin Lymphoma (cHL) from the US Food and Drug Administration (FDA) and the European Commission (EC), expanding its use for both paediatric and adult patients. The FDA has approved Opdivo, along with doxorubicin, vinblastine, and dacarbazine (AVD) for adults and paediatric patients aged 12 years and above who have not previously been treated for Stage III or IV cHL. In the European Union (EU), the EC granted approval for Opdivo in combination with brentuximab vedotin to treat children aged five years and above, adolescents, and adults up to 30 years who have relapsed or refractory cHL following one previous line of treatment. The FDA approval is supported by data from the Phase III SWOG 1826 study, which assessed Opdivo plus AVD in adults and children aged 12 years or older. A submission based on this trial is under review by the European Medicines Agency (EMA). The EC approval is based on the Phase II CheckMate -744 trial, assessing Opdivo plus brentuximab vedotin in paediatric patients aged five years and above, adolescents and adults up to 30 years. BMS oncology commercialisation senior vice-president Monica Shaw said: “These approvals represent a defining moment for people living with classical Hodgkin lymphoma. In the US, we are particularly proud that Opdivo in combination with AVD now stands as an immunotherapy combination available for adults and paediatric patients, ages 12 and older, with previously untreated advanced disease. “Concurrently, in the EU, Opdivo in combination with brentuximab vedotin has also achieved a milestone as the first immunotherapy combination for certain relapsed or refractory patients. These milestones reflect our continued commitment to advancing science that meaningfully improves the lives of patients and families worldwide.” Earlier this month, BMS received the FDA approval for Sotyktu (deucravacitinib), an oral selective tyrosine kinase 2 (TYK2) inhibitor, to treat adults with active psoriatic arthritis (PsA).

The US FDA issued an approval notice for Opdivo (nivolumab) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for adult and pediatric patients aged 12 years and older with previously untreated, Stage III or IV classical Hodgkin lymphoma (cHL). The approval, granted to Bristol Myers Squibb (BMS), makes nivolumab the first PD-1 checkpoint inhibitor authorized for frontline use in advanced cHL, a disease that affects approximately 8,500 to 9,000 people annually in the United States. Concurrently, the FDA converted nivolumab’s prior accelerated approvals from 2016 and 2017 for relapsed or refractory cHL to traditional approvals. The application received priority review and orphan drug designation, and was reviewed under Project Orbis in collaboration with regulatory agencies in Israel, Australia, Canada, and Switzerland. The approval covers nivolumab at 240 mg for adults and pediatric patients weighing 40 kg or more, or 3 mg/kg for those under 40 kg, administered intravenously on Days 1 and 15 of each 28-day cycle for up to six cycles in combination with AVD. Primary G-CSF prophylaxis is recommended starting in Cycle 1. The traditional approval conversion applies to two previously accelerated indications in adults with relapsed or refractory disease: after autologous hematopoietic stem cell transplantation and brentuximab vedotin, and after three or more lines of systemic therapy including autologous transplantation. The approval rests on results from SWOG S1826 (Study CA209-8UT), a randomized, open-label, multicenter Phase III trial that enrolled 994 patients aged 12 years and older with previously untreated Stage III or IV classical Hodgkin lymphoma. Patients were randomized 1:1 to receive either nivolumab plus AVD or brentuximab vedotin plus AVD for six cycles. The primary endpoint was investigator-assessed progression-free survival. The nivolumab arm demonstrated a hazard ratio of 0.42 (95% CI: 0.27–0.67; p<0.0001), corresponding to a 58% reduction in the risk of progression or death. Median progression-free survival was not reached in either arm after a median follow-up of 13.7 months. At a median follow-up of 36.7 months, deaths occurred in 1.8% of patients receiving nivolumab plus AVD compared with 3.4% in the brentuximab vedotin arm. Serious adverse reactions occurred in 39% of patients in the nivolumab arm, with immune-mediated adverse reactions reported in 9% of patients, of which 2.7% were Grade 3 or 4. This approval alters the treatment landscape for advanced cHL, where brentuximab vedotin (Adcetris, Seagen/Pfizer) combined with AVD has been an important frontline standard, particularly in advanced-stage disease, since its approval in 2018 based on the ECHELON-1 trial. The SWOG S1826 trial was designed as a direct head-to-head comparison between the two regimens, and the magnitude of the progression-free survival difference was substantial. For BMS, the approval extends Opdivo’s reach into a new line of therapy for a disease where it previously held indications only in the relapsed or refractory setting. Classical Hodgkin lymphoma disproportionately affects adolescents and young adults, a population for whom long-term treatment toxicity is a persistent concern. Both the nivolumab and brentuximab vedotin combination regimens use AVD rather than the older ABVD backbone, eliminating bleomycin and its associated pulmonary toxicity. The field continues to evolve, with investigational approaches including CD30-directed CAR-T cell therapies, dual checkpoint blockade, and anti-CD25 antibody-drug conjugates such as camidanlumab tesirine (ADC Therapeutics) in development for relapsed or refractory disease. An open question is how to manage patients who relapse after receiving PD-1 inhibitor-based frontline therapy, a clinical scenario that will become more common as this regimen enters routine practice. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website