Brentuximab Vedotin Combination Shows Promise in Hodgkin Lymphoma

Ann LaCasce, MD

Ninety-six percent of patients with relapsed or refractory Hodgkin lymphoma who received treatment with the combination of brentuximab vedotin and bendamustine responded to treatment without experiencing dose-limiting toxicity, according to findings from a phase I/II study presented at the 2014 ASH Annual Meeting.

"Both the overall response rate and complete remission rates are significantly higher with the combination than with either agent alone,” lead author Ann LaCasce, MD, a lymphoma specialist at Dana-Farber Cancer Institute in Boston, said in an interview with OncLive. “The combination has a manageable safety profile with premedication for infusion-related reactions.”

Both brentuximab vedotin and bendamustine have demonstrated single-agent activity in relapsed/refractory Hodgkin lymphoma, each achieving a complete response rate in about a third of patients. The individual drugs have manageable safety profiles. The drugs also have non-overlapping mechanisms of action.

The phase I/II study sought to discover if the combination of these agents could induce high levels of complete response. The phase I portion enrolled 10 patients with relapsed/refractory Hodgkin lymphoma and addressed the safety of using the drugs in combination and finding an optimal dose.

In the phase II portion, 44 patients were treated with bendamustine 90 mg/m² and brentuximab vedotin 1.8 mg/kg. Of the 54 patients who were enrolled, 27 had primary refractory disease and relapsed disease. Among the patients in relapse, 17 had a remission duration >1 year, and the remaining 10 had a remission duration ≤1 year. A majority of patients received the ABVD regimen as first-line therapy, said LaCasce.

The combination led to complete responses in 83% of 48 evaluable patients and an additional 13% had partial responses. All but six of the 40 complete responses occurred at the cycle 2 restaging, said LaCasce. Twenty patients went on to undergo an autologous stem cell transplant following the 2nd and third cycle. Thirteen patients went on to receive brentuximab vedotin monotherapy.

“The therapy has no adverse impact on stem-cell mobilization or engraftment to date,” said LaCasce. “This combination represents a promising salvage regimen for patients with Hodgkin lymphoma who have relapsed and refractory disease after frontline therapy.”

Among 33 patients who underwent stem-cell mobilization, only one did not have successful first-line mobilization. Additionally, 17 of the 33 patients underwent stem-cell mobilization after completing two cycles of the combination therapy. The median time to platelet and neutrophil engraftment was less than 2 weeks.

The median progression-free survival (PFS) has not yet been reached. Thus far, progression has occurred in four patients and one patient died after stem-cell transplant. The median duration of response also has not been reached.

Overall, 96% of patients had treatment-emergent adverse events, including serious adverse events in 22% and grade ≥3 adverse events in 41%. The main toxicities observed were infusion-related, including dyspnea (15%), chills (13%), and flushing (13%). Additionally, hypotension requiring vasopressor support occurred during the trial.

“The majority of reactions occurred within 24 hours of the cycle 2 infusion and were considered related to both agents,” said LaCasce. "There was some infusion-related toxicity that we saw when the two drugs were added together that was a little unexpected. The protocol was amended midway through to require corticosteroids and antihistamines, which really tempered those reactions."

Following the protocol amendment, the frequency of reactions dropped off substantially. The incidence of any-grade infusion-related reaction declined from nearly 60% to approximately 50%. The rate of serious infusion-related adverse events declined significantly from over 20% to nearly none.

"Hopefully, with longer follow-up, this could become a standard salvage chemotherapy regimen, to get people to transplant," LaCasce concluded.

LaCasce A, Bociek RG, Matous J, et al. Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy. Presented at: 2014 ASH Annual Meeting; December 6-9, 2014; San Francisco, CA. Abstract 293.

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