ICML 2017: Brentuximab Vedotin in Combination With Nivolumab in Patients With Relapsed or Refractory Hodgkin Lymphoma
An updated interim analysis from an ongoing phase I/II clinical trial evaluating brentuximab vedotin (Adcetris) and nivolumab (Opdivo) in relapsed or refractory classical Hodgkin lymphoma was presented at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (Abstract 74). Brentuximab vedotin is an antibody-drug conjugate directed to CD30, a defining marker of classical Hodgkin lymphoma. Nivolumab is a programmed cell death protein 1 (PD-1) immune checkpoint inhibitor that is designed to help restore antitumor immune response.
“The phase I/II study combining the antibody-drug conjugate brentuximab vedotin with the PD-1 immune checkpoint inhibitor nivolumab is a promising investigational approach, as it combines a targeted therapy with a therapy designed to activate the immune system, and the combination may have additive activity,” said Alex Herrera, MD, lead trial investigator and Assistant Professor at City of Hope in Duarte, California. “The interim results support further exploration of this novel regimen, free of traditional chemotherapy.”
“We are evaluating brentuximab vedotin in novel combinations in order to identify potential treatment regimens for patients with CD30-expressing lymphomas,” said Jonathan Drachman, MD, Chief Medical Officer and Executive Vice President, Research and Development, Seattle Genetics. “We are pleased to share updated interim results from this ongoing phase I/II clinical trial evaluating brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma patients. Since our first patient treated with the combination regimen, the data continue to demonstrate encouraging activity with an acceptable safety profile. These updated data support findings first presented at the 2016 American Society of Hematology Meeting. We have nearly doubled the number of patients in our trial evaluating the brentuximab vedotin/nivolumab combination strategy and recently announced a collaboration with [Bristol-Myers Squibb] to initiate a … phase III clinical trial in relapsed [Hodgkin lymphoma] patients in mid-2017.”
Study Findings
Data were reported from 62 patients with relapsed/refractory classical Hodgkin lymphoma who, after failure of front-line therapy, received the combination regimen of brentuximab vedotin plus nivolumab. Patients were treated once every 3 weeks with up to 4 cycles of combination therapy. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant.
The median age of patients was 36 years. About 45% of patients had primary refractory disease, and 55% had disease progression after responding to front-line therapy, among whom 90% received standard-of-care front-line treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).
Key findings presented include:
- Of 59 response-evaluable patients, 50 patients (85%) had an objective response, including 37 patients (63%) with a complete response and 13 patients (22%) with a partial response. Among all patients, 5 (8%) had stable disease and 4 (7%) had progressive disease.
- Of the 62 patients enrolled, 61 (98%) received 1 or more dose of the study therapies. No patients remain on treatment—58 (94%) have finished treatment and 4 (6%) discontinued treatment prior to its completion. At the time of data analysis in the ongoing trial, 37 patients (60%) initiated an autologous stem cell transplant and 12 (19%) received an alternative salvage therapy subsequent to combination therapy. No unusual posttransplant adverse events were reported. Preliminary analysis shows no impact of brentuximab vedotin plus nivolumab on stem cell mobilization or engraftment.
- Prior to stem cell transplant, the most common adverse events of any grade occurring in more than 25% of patients were nausea (56%); fatigue (43%); infusion-related reactions (36%); pruritus (31%); headache (28%); and diarrhea, rash, and vomiting (all at 26%). Treatment-related serious adverse events occurred in 5 patients (8%), including pneumonitis and pyrexia (2 patients each) and colitis, malaise, nausea, pneumonia, respiratory failure and sepsis (1 patient each).
- Infusion-related reactions were observed in 41% of patients. All infusion-related reactions were grade 3 or less, with the rate of grade 3 infusion-related reactions less than 5%.
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