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KEYNOTE-013: Pembrolizumab active, safe in pre-treated Hodgkin’s lymphoma
The monoclonal antibody pembrolizumab demonstrated considerable clinical benefit in heavily pretreated patients with classical Hodgkin’s lymphoma.
Antibody-mediated blockade of programmed cell death-1 (PD-1) has proven effective for treatment of patients with solid tumors, and it is under evaluation in patients with blood cancers.
Classical Hodgkin’s lymphoma may represent a uniquely vulnerable target for PD-1 blockade, according to Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at Memorial Sloan Kettering Cancer Center and a HemOnc Today Editorial Board member.
The reason is that there is overexpression of PD-L1 and PD-L2 in classical Hodgkin’s lymphoma.
In the KEYNOTE-013 trial, Moskowitz and colleagues evaluated pembrolizumab (MK-3475, Merck) in 29 patients with relapsed or refractory classical Hodgkin’s lymphoma.
“Pembrolizumab has a high affinity for the PD‐1 receptor, with a dual ligand blockade of PD‐L1 and PD‐L2,” Moskowitz said.
All patients either relapsed after or failed to respond to treatment with brentuximab vedotin (Adcetris, Seattle Genetics). Sixty-seven percent of patients failed prior autologous stem cell transplantation. All patients had adequate performance status and organ function.
Patients received 10 mg/kg IV pembrolizumab every 2 weeks until confirmed tumor progression, excessive toxicity or completion of 2 years of therapy. Safety, tolerability and complete remission served as the primary outcome measures.
Researchers reported a 66% overall response rate, a 21% complete response rate and an 86% clinical benefit rate.
The median duration of response has not been reached, according to Moskowitz.
“A number of patients had stable disease,” he said. “I actually think stable disease is quite important when these checkpoint inhibitors are administered.”
One patient each developed grade 3 axillary pain, hypoxia, joint swelling and pneumonitis. Researchers reported no grade 4 treatment-related adverse events.
“These results are particularly compelling since they are demonstrating complete responses to a drug in a patient population who had failed all other therapies. This was their last chance,” Moskowitz said. “It will be important to further evaluate this drug in combination with others, or perhaps even as a maintenance treatment, to enhance the post-transplant immune response.”
Reference:
Moskowitz CW. Abstract #290.
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Disclosure: Moskowitz reports research funding from Merck.
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