Up to 8 cycles of brentuximab vedotin plus nivolumab is “highly active” as post-transplant consolidation for patients with high-risk, relapsed or refractory classic Hodgkin lymphoma, according to researchers.
The researchers observed high rates of progression-free survival (PFS) and overall survival (OS) in these patients, most of whom had previously received brentuximab vedotin and anti-PD-1 therapy. The results were published in The Lancet Haematology.
This phase 2 trial (ClinicalTrials.gov Identifier: NCT03057795) included 59 patients with a median age of 30 years. Most patients (n=53) had primary refractory or early relapsed classic Hodgkin lymphoma. Thirty patients had previously received brentuximab vedotin, and 25 had previously received PD-1 blockade.
Patients started brentuximab vedotin plus nivolumab a median of 54 days after autologous hematopoietic stem cell transplant (HSCT). They received a median of 8 treatment cycles.
All but 6 patients were in complete response after HSCT. The 6 patients were in partial response after HSCT, but 5 of them achieved a complete response after brentuximab vedotin plus nivolumab. The sixth patient remained in partial response until disease progression at 16 months after study enrollment.
The median follow-up was 29.9 months. The 18-month PFS rate was 94%, and the 24-month PFS rate was 92%. The 24-month OS rate was 98%.
“Brentuximab vedotin plus nivolumab was highly active post-autologous HSCT consolidation for patients with high-risk relapsed or refractory classic Hodgkin lymphoma, most of whom had previous exposure to either brentuximab vedotin or PD-1 blockade,” the researchers wrote.
A total of 14 patients (24%) discontinued both study drugs after a median of 4 cycles. Six patients discontinued due to adverse events (AEs), including 3 due to pneumonitis, 1 due to abdominal pain, 1 due to myalgia, and 1 due to rash. Discontinuation was due to voluntary withdrawal in 6 patients, 1 patient was lost to follow-up, and 1 patient died from Pneumocystis jirovecii pneumonia.
There were 8 patients who discontinued brentuximab vedotin early but continued with nivolumab treatment. Reasons for discontinuation included grade 3 peripheral neuropathy (n=2), grade 2 peripheral neuropathy (n=2), carpal tunnel syndrome (n=1), gastrointestinal AEs (n=2), and an infusion-related reaction (n=1).
There were 7 patients who discontinued nivolumab early but continued treatment with
brentuximab vedotin. Reasons for discontinuation included pneumonitis (n=2), colitis (n=1), elevated bilirubin (n=1), abnormal aminotransaminases (n=1), pneumonia with
elevated creatinine (n=1), and hypotension with fever (n=1).
In the overall cohort, the most common AEs were sensory peripheral neuropathy (53%), neutropenia (42%), fatigue (37%), diarrhea (29%), arthralgia (25%), nausea (24%), elevated AST (24%), and myalgia (20%). The most common grade 3 or higher AEs were neutropenia (31%) and pneumonitis (7%).
“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,” the researchers wrote. “Our findings support further evaluation of combination immunotherapy as consolidation to improve outcomes in patients with classic Hodgkin lymphoma undergoing autologous HSCT.”
Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Herrera AF, Chen L, Nieto Y, et al. Brentuximab vedotin plus nivolumab after autologoushaematopoietic stem-cell transplantation for adult patients with high-risk classic Hodgkin lymphoma: A multicentre, phase 2 trial. Lancet Haematol. Published online November 17, 2022. doi:10.1016/S2352-3026(22)00318-0
This article originally appeared on Cancer Therapy Advisor