In a Phase III trial, Bristol Myers Squibb's (BMS) Opdivo, when combined with doxorubicin, vinblastine, and dacarbazine (AVD), demonstrated superior progression-free survival compared to Pfizer and Seagen’s Adcetris plus AVD in patients with newly diagnosed stage 3 or 4 Hodgkin's lymphoma. The findings, published in The New England Journal of Medicine, highlight the potential of Opdivo as a first-line treatment option for this patient population.
The study evaluated the efficacy of Opdivo, a PD-1 blocker, in combination with the AVD regimen against Adcetris plus AVD, with the primary endpoint being progression-free survival. After a median follow-up of 12.1 months, patients receiving Opdivo experienced a 52% reduction in the risk of disease progression or death (p=0.001).
Long-Term Survival Analysis
Further analysis after 2.1 years of follow-up revealed a 92% progression-free survival rate in the Opdivo arm, compared to 83% in the Adcetris arm. This sustained benefit underscores the potential of Opdivo to improve long-term outcomes for patients with advanced Hodgkin's lymphoma.
Minimizing Toxicity
Study lead Jonathan Friedberg, director of the Wilmot Cancer Institute at the University of Rochester Medical Center, emphasized the trial's goal of improving cure rates while minimizing side effects and long-term toxicities. The study reported that immune-related toxicities were infrequent in the Opdivo group, and patients on the Adcetris regimen were more likely to discontinue the study due to adverse events.
Friedberg noted the potential for fewer late-term complications such as breast cancers, infertility, and heart disease, particularly benefiting pediatric patients who often undergo radiation therapy, which carries a significant burden of side effects.
Mechanism of Action
Opdivo is a human IgG4 monoclonal antibody that targets and binds to the PD-1 ligand, blocking its interaction with its receptor. This mechanism prevents cancer cells from suppressing the body’s anti-tumor response, thereby enhancing the immune system's ability to fight the lymphoma.
Current Approvals and Future Implications
Opdivo is currently approved for various cancers, including melanoma, lung cancer, and renal cell carcinoma. In Hodgkin’s lymphoma, it is approved for patients who relapse or progress after autologous hematopoietic stem cell transplantation plus Adcetris, or after at least three lines of systemic therapy. It is not yet approved as a first-line treatment for Hodgkin’s lymphoma.
Friedberg anticipates that Opdivo will soon be integrated into treatment guidelines and standard care for stage 3 or 4 Hodgkin lymphoma, given its existing approvals for other indications. The FDA will ultimately determine whether Opdivo should be added as a standard first-line treatment.
