Brentuximab combinations highly active in Hodgkin lymphoma
Investigators therefore hypothesized that brentuximab in combination with bendamustine could induce more CRs in HL patients with relapsed or refractory disease after frontline therapy.
Ann LaCasce, MD, of Dana-Farber Cancer Institute in Boston, presented the data at ASH as abstract 293.*
Ten patients were enrolled in the phase 1 portion of the study to determine the optimal dose level of bendamustine and to assess safety and tolerability.
No dose-limiting toxicities were observed. So the investigators used bendamustine at 90 mg/m2 and brentuximab at 1.8 mg/kg. Patients received a median of 2 cycles (range, 1 to 6) of combination therapy.
Patients had the option to proceed to an autologous stem cell transplant at any time after cycle 2 and could receive brentuximab monotherapy thereafter for up to 16 total doses.
The phase 2 expansion portion enrolled 44 patients and assessed the best response, duration of response, and progression-free survival.
Results
Patients were a median age of 37 years (range, 27 to 51), and 57% were male. Ninety-eight percent were ECOG status 0 or 1, and 54% had stage III or IV disease at diagnosis.
The majority of patients had received ABVD as frontline therapy, Dr LaCasce pointed out.
The most common treatment-emergent adverse event was infusion-related reactions, accounting for 96% of the events. Dyspnea (15%), chills (13%), and flushing (13%) were the most common symptoms, and hypotension requiring vasopressor support also occurred.
Most reactions occurred within 24 hours of the cycle 2 infusion and were considered related to both agents. However, delayed hypersensitivity reactions also occurred, Dr LaCasce said, the most common being rash in 14 patients up to 22 days after infusion.
“Based on the number of infusion-related reactions after 24 patients, the protocol was amended to require mandatory corticosteroids and anthistamine premedication,” Dr LaCasce explained. “[T]his resulted in a significant decrease in the severity of the infusion-related reactions.”
The best clinical response for the 48 evaluable patients was 83% CR and 13% partial remission, for an objective response rate of 96%.
The median progression-free survival has not yet been reached, and the combination has had no negative impact on stem cell mobilization or engraftment to date.
The response rate compares very favorably to historical data, Dr LaCasce said, and the combination represents a promising salvage regimen for HL patients. 
*Data in the presentation differ from the abstract.
