Keytruda Improves Progression-Free Survival in Subset of Patients With Relapsed/Refractory Hodgkin Lymphoma

Keytruda (pembrolizumab) led to greater improvements in progression-free survival compared with Adcetris (brentuximab vedotin) for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma who were ineligible for autologous hematopoietic stem cell transplantation or relapsed after the transplantation, according to a study published in Lancet Oncology.

“Historically, patients with primary refractory disease or those who do not receive autologous (hematopoietic stem cell transplantation) owing to advanced age, comorbidities, stem cell mobilization failure or chemo-resistant disease have poorer response rates and outcomes compared with patients with chemo-sensitive disease and those who receive autologous stem cell transplantation,” the study authors wrote. “Our results suggest that (Keytruda) is an effective treatment option in both of these difficult-to-treat patient populations.”

Adcetris is an antibody-drug conjugate that targets the protein CD30 without harming other nearby cells. In a previous study, Adcetris led to a response in 75% of patients with relapsed or refractory classical Hodgkin lymphoma after autologous hematopoietic stem cell transplantation, although 42% of patients experienced peripheral neuropathy (pain, tingling, numbness, muscle weakness or swelling related to nerves) and the median progression-free survival was 5.6 months.

“Although (Adcetris) has become an important component of therapy for classical Hodgkin lymphoma, patients would benefit from additional approaches that further improve progression-free survival and minimize toxic effects that can affect quality of life such as peripheral neuropathy,” the study authors wrote in the introduction.

Keytruda is an anti-PD-1 antibody approved for the treatment of patients with classical Hodgkin lymphoma and has been shown to provide long-term efficacy in patients with relapsed or refractory disease. In this phase 3 trial, researchers compared Keytruda with Adcetris with regards to efficacy and safety in this specific patient population.

To do so, researchers assessed patients with relapsed or refractory classical Hodgkin lymphoma who were either ineligible for an autologous hematopoietic stem cell transplantation or relapsed after the transplantation. Patients were assigned 200 mg of Keytruda intravenously every three weeks (151 patients; median age, 36 years; 56% men) or 1.8 mg/kg of Adcetris intravenously every three weeks (153 patients; median age, 35 years; 59% men). Treatment was administered for up to 35 weeks or until unacceptable toxic effects, documented disease progression or a decision made by the investigator.

Factors of interest in this study included progression-free survival (time from treatment assignment to disease progression or all-cause death) and safety. The median time from treatment assignment to when data were cutoff for this trial was 25.7 months.

During the trial, the median progression-free survival for patients assigned Keytruda was 13.2 months compared with 8.3 months for those assigned Adcetris.

The most common severe or life-threatening side effects related to either Keytruda or Adcetris included pneumonitis (inflamed lung tissue; 4% versus 1%, respectively), decreased neutrophil count (1% versus 5%), abnormally low counts of neutrophils (2% versus 7%) and peripheral neuropathy (1% versus 3%).

“The safety profile of (Keytruda) was better than that for (Adcetris) in this heavily pretreated patient population and was generally consistent with previously reports,” the study authors wrote. “(Side effects) were predictable, reversible and manageable. Pneumonitis was uncommon and could be managed safely by withholding the drug and instituting appropriate treatment as needed.”

Several serious side effects related to treatment was observed in 16% of patients assigned Keytruda and 11% of patients assigned Adcetris. One death related to treatment occurred in the Keytruda group and was due to pneumonia.

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