Brentuximab Vedotin plus Nivolumab Yields High Complete Responses in Relapsed or Refractory Hodgkin Lymphoma
Atlanta, GA—Interim results from a phase 1/2 study of the combination of brentuximab vedotin (Adcetris) and nivolumab (Opdivo) have demonstrated a high overall response rate (ORR) in patients with relapsed or refractory Hodgkin lymphoma. According to data presented at ASH 2017, 83% of patients responded to the combination, which included a 62% rate among efficacy-evaluable patients.
“These data suggest the combination of brentuximab vedotin and nivolumab is a well-tolerated and active salvage therapy with a high rate of complete response that has no adverse impact on stem-cell collection,” said Alex F. Herrera, MD, Assistant Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.
“The safety and activity of this novel combination support further exploration in an ongoing pivotal phase 3 trial in patients with relapsed or refractory Hodgkin lymphoma who have already received or are considered ineligible for autologous stem-cell transplant [ASCT].”
Brentuximab vedotin and nivolumab are effective single-agent treatments for relapsed or refractory Hodgkin lymphoma. Brentuximab vedotin is believed to activate the patient’s immune system and initiate an antitumor immune response through the induction of immunogenic cell death, whereas nivolumab blocks the PD-1 receptor, inhibits binding of PD-1 ligands, and restores an effective antitumor immune response.
The phase 1/2, open-label, multicenter trial enrolled 62 adults with relapsed or refractory classical Hodgkin lymphoma. Patients were excluded if they previously received salvage therapy; brentuximab vedotin; immune-oncology therapy affecting the PD-1, CTLA4, or CD137 pathways; or stem-cell transplant. The study’s primary end points were safety, the incidence and severity of adverse events, and complete response rate after study completion.
The patients received brentuximab vedotin in combination with nivolumab every 3 weeks (1 cycle) for up to 12 weeks (4 cycles). After completion of the therapy, the patients were eligible to undergo ASCT.
Overall, 60 (98%) patients had adverse events before undergoing ASCT or receiving salvage therapy after treatment. The majority (66%) of these adverse events were grade 1 or 2, but 19 (31%) were grade ≥3. Infusion-related reactions were reported by 27 (44%) patients, with 25 (41%) of these occurring during infusion with brentuximab vedotin, most often during cycle 2.
“Pretreatment with low-dose steroid and antihistamine did not impact the frequency or severity of these reactions, which caused an interruption of infusion in 16 patients,” Dr Herrera said. “However, no patients discontinued treatment due to an infusion-related reaction.”
Although 5 patients required systemic steroids for the treatment of an immune-related adverse event, no patients discontinued treatment because of these events.
The ORR with the combination treatment as first salvage therapy was 83%, and the complete response rate was 62%.
“The combination of BV [brentuximab vedotin] and nivolumab did not appear to impact stem-cell mobilization and collection yields or engraftment,” said Dr Herrera. “Patients did not appear to have increased toxicity during or after the transplant period.”
In addition, the combination resulted in increased numbers of circulating T-cells, increased innate and adaptive immune-activating cytokines and chemokines, and increased ability of memory T-cells to mount an immune response.
“The encouraging activity of BV plus nivolumab will be further evaluated in multiple settings, including a pivotal phase 3 trial in patients with advanced Hodgkin lymphoma who are ineligible for ASCT or after failure of ASCT,” Dr Herrera concluded.