Post-HSCT Brentuximab Vedotin Plus Nivolumab Highly Effective in Hodgkin Lymphoma

Brentuximab vedotin (Adcetris) in combination with nivolumab (Opdivo) after autologous hematopoietic stem-cell transplantation (HSCT) resulted in improved outcomes in patients with high-risk relapsed or refractory classic Hodgkin lymphoma, many of whom had previously been exposed to either brentuximab vedotin or PD-1 blockade, a small multicenter phase II trial showed.

Among 59 patients, the 18-month progression-free survival (PFS) rate was 94% (95% CI 84-98), meeting the study’s primary endpoint, reported Alex F. Herrera, MD, of City of Hope Medical Center in Duarte, California, and colleagues.

Furthermore, the 24-month PFS rate was 92% (95% CI 81-97), and the 24-month overall survival rate was 98% (95% CI 88-100), they noted in Lancet Haematology.

Intensifying consolidation by adding nivolumab to brentuximab vedotin yielded these promising results despite a shorter planned duration of therapy (eight vs 16 cycles), Herrera and team said. However, they also pointed out that more toxic effects were observed in the study patients compared with those taking the combination in the pre-HSCT setting, including a higher rate of immune-related adverse events that required systemic corticosteroids.

“On the basis of the toxic effects observed in our study, brentuximab vedotin plus nivolumab consolidation might be best suited to the highest-risk patients, wherein the balance of cost, toxicity, and efficacy might favor more intensive consolidation to prevent relapse,” they wrote.

In an accompanying commentary, Andrea Gallamini, MD, of Centre Antoine Lacassagne in Nice, France, suggested that the study’s clinical value was demonstrated by the effect that a rescue treatment had on long-term disease control after first treatment failure (which he estimated at 15%).

“Whether results obtained by Herrera and colleagues will be confirmed by a longer follow-up and in a larger series of patients, a second-line treatment that is able to induce prolonged disease remission in more than 95% of the patients is a milestone achievement in the overall treatment of Hodgkin lymphoma,” Gallamini concluded.

Herrera and team noted that the previous AETHERA trial showed that post-autologous HSCT consolidation with brentuximab vedotin for a planned 16 cycles resulted in extended PFS compared with placebo in patients with high-risk relapsed or refractory Hodgkin lymphoma undergoing autologous HSCT.

They also pointed out that brentuximab vedotin and nivolumab were found to be safe and effective as a combination salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma.

Thus, they wrote, their primary objective was to improve outcomes of post-HSCT consolidation by adding PD-1 blockade to brentuximab vedotin, while also minimizing the toxic effects of brentuximab vedotin with a shorter duration of therapy (eight cycles, which was the the previously studied duration of anti-PD-1 monotherapy post-HSCT consolidation).

In this multicenter study, eligible patients were 18 and older, had histologically confirmed classic Hodgkin lymphoma, and had one or more of these high-risk features:

• Primary refractory classic Hodgkin lymphoma
• Relapsed classic Hodgkin lymphoma within 1 year of completing initial therapy
• Extranodal involvement or B symptoms at relapse
• More than one salvage regimen used before autologous HSCT

Patients received brentuximab vedotin (1.8 mg/kg) and nivolumab (3 mg/kg) intravenously starting 30 to 60 days after autologous HSCT on day 1 of each 21-day cycle for up to eight cycles.

Of the 59 patients analyzed, 21 had one risk factor, while 38 had two or more risk factors. The 24-month PFS rate according to the number of risk factors was 94% in patients with one risk factor, 96% in patients with two risk factors, and 85% in patients with three or more risk factors. Median follow-up was 29.9 months.

Herrera and colleagues pointed out that a key difference between their study and AETHERA was that they included patients with previous exposure to brentuximab vedotin or PD-1 blockade as long as their disease did not progress on those treatments.

Since brentuximab vedotin has been studied as an initial and salvage treatment for classic Hodgkin lymphoma, and is approved for frontline use in advanced-stage classic Hodgkin lymphoma, the authors noted that it has been increasingly used before autologous HSCT.

This study included 30 patients who had received previous brentuximab vedotin and 25 patients who had received previous PD-1 blockade. “Therefore, a patient who responds to brentuximab vedotin or PD-1 blockade, or both, during salvage before autologous HSCT would be a reasonable candidate for post-HSCT consolidation with brentuximab vedotin plus nivolumab,” Herrera and team wrote.

As for safety, 14 patients discontinued treatment early (both brentuximab vedotin and nivolumab) after a median of four cycles. The most common adverse events were sensory peripheral neuropathy (53%) and neutropenia (42%). Immune-related adverse events requiring corticosteroids occurred in 29% of patients. There were no treatment-related deaths.