Opdivo Shows Benefits in Heavily Pretreated Classical Hodgkin Lymphoma

A phase 2 trial of nivolumab (Opdivo) in heavily pretreated classical Hodgkin lymphoma (cHL) patients showed benefits from treatment.

The PD-1 immune checkpoint inhibitor attaches to the checkpoint receptor PD-1 that is expressed on activated T cells to block PD-L1 and PD-L2 from binding. This action stops suppressive signaling in the PD-1 pathway on the immune system, which includes inhibiting an anti-tumor immune response.

The multi-cohort, non-comparative, international, multicenter, single-arm, pivotal phase 2 trial CheckMate-205 evaluated Opdivo in patients with cHL. All patients in cohort B previously failed auto-HSCT and subsequent brentuximab vedotin.

The median amount of prior therapy was 4, and there were 49% of participants who received at least 5 previous lines of therapy. Patients were given 3-mg/kg of Opdivo intravenously every 2 weeks until disease progression or unacceptable toxicity.

The study was assessed by the Independent Radiologic Review Commission (IRRC), who determined the primary endpoint of objective response rate (ORR) and secondary endpoints for duration of objective response, complete and partial remission rates, duration of complete and partial remission. Based on investigator assessment, the secondary endpoints included objective response and duration of objective response.

The exploratory endpoints determined by the IRRC were progression free survival, overall survival, safety and tolerability, and quality-of-life.

The results of the study found that the ORR per IRRC was 66.3% (95% CI: 54.8-76.4). The median time to response was 2.1 months, and the estimated median duration of remission was 7.8 months (95% CI: 6.6-NE). The majority of responses were 62.3% and was ongoing at the time of analysis.

The exploratory analysis revealed that more than two-thirds (72.1%) of patients who did not respond to the most recent prior treatment with brentuximab vedotin did not respond to Opdivo. The safety of Opdivo in the trial was consistent with previously reported data for this tumor type.

The most common drug-related adverse events were fatigue, infusion-related reaction, rash, arthralgia, pyrexia, nausea, diarrhea, and pruritus. Grade 3 and 4 AEs occurred in 40% of patients, while grade 5 occurred in 1%.

“There is currently no standard treatment option for classical Hodgkin lymphoma patients who have relapsed or whose disease has progressed after auto-HSCT and post-transplantation brentuximab vedotin,” said lead study investigator Andreas Engert, MD. “We are encouraged by the objective response rates and that the majority of responses were ongoing at the time of analysis in the CheckMate -205 trial evaluating Opdivo in these heavily pre-treated patients.”

The study’s finding was presented at the Congress of European Hematology Association (EHA) in Denmark.

“Classical Hodgkin lymphoma is a disease that disproportionately impacts young people, and there is a significant unmet need for patients who are not cured by the current standard-of-care treatments and who have a poor prognosis and very limited options,” said Jean Viallet, MD. “The data presented at EHA demonstrate that Opdivo is an important treatment option for patients whose disease has progressed after auto-HSCT and post-transplantation brentuximab vedotin.”