Early Study Shows Keytruda Active in Hodgkin Lymphoma

An early study in patients with Hodgkin lymphoma that had progressed on several lines of treatment found that the immunotherapy Keytruda (pembrolizumab) elicited a remarkable response. Treatment with the PD-1 inhibitor Keytruda generated responses in 66 percent of patients with heavily pretreated classical Hodgkin lymphoma (cHL), according to preliminary results of an early phase 1b study reported at the annual meeting of the American Society of Hematology (ASH) held in San Francisco.

Of the 29 evaluable patients with cHL who received Keytruda, six patients experienced complete remission while 13 patients achieved a partial remission, lead researcher Craig H. Moskowitz said during a press briefing. Among the remaining participants, six patients had stable disease while four individuals experienced progressive disease.

The patients included in the trial had received a median of four prior lines of therapy. In total, 69 percent of patients had relapsed following stem cell transplant and, by trial design, all patients had failed treatment with Adcetris (brentuximab vedotin). Patients ranged in age from 20 to 67 years with a median age of 32 years.

“Pembrolizumab, I believe, has excellent activity in patients with Hodgkin lymphoma in a cohort of patients who all previously failed brentuximab vedotin,” said Moskowitz, clinical director in the Division of Hematologic Oncology at Memorial Sloan Kettering Cancer Center in New York City.

The patients with cHL are part of a broader group of participants in the ongoing KEYNOTE-013 trial, which is seeking to recruit approximately 100 people with hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma and myelodysplastic syndrome.

Moskowitz said the activity that Keytruda demonstrated in this group of patients should encourage pharmaceutical developers to continue to explore PD-1 inhibitors in a “variety of subsets of patients with classical Hodgkin lymphoma.”

In September, Keytruda became the first PD-1 inhibitor to be approved when it was given the green light for unresectable or metastatic melanoma that has progressed after prior therapies. The drug is being studied in more than 30 types of cancers, including bladder, non-small cell lung and head and neck.

Keytruda is a monoclonal antibody that stimulates an anti-tumor immune response by hindering the PD-1 receptor from interacting with its ligands, PD-L1 and PD-L2, which is activity that acts as a brake on the patient’s immune system.

During the trial, patients were treated with Keytruda intravenously every two weeks until progression, excessive toxicity or completion of two years of treatment. Primary endpoints of the trial focused on safety, tolerability and complete remission.

Response assessment was conducted at week 12 and every eight weeks thereafter. Results were reported from the time of analysis, which was in November. In addition to 20 patients whose disease relapsed after transplant, the cohort included eight patients who were ineligible for transplant and one patient who refused transplant.

The overall response rate (ORR) for the entire group was 66 percent; among those who had previously failed transplant, the ORR reached 75 percent and four of these patients achieved a complete remission.

Keytruda was extremely well tolerated, Moskowitz said. The most commonly reported adverse events were mild respiratory events (20 percent) and thyroid disorders (20 percent).

“I think the safety profile of these drugs are really quite good—very little grade 3/4 toxicity,” Moskowitz said. No severe treatment-related adverse events or treatment-related deaths were reported. In total, three patients experienced four adverse events of grade 3 or greater (axillary pain, hypoxia, joint swelling and pneumonitis).

The median time to response was 12 weeks, while the median duration of response has not yet been reached. As of November 17, 89 percent of patients had ongoing responses. While four patients experienced disease progression, all four experienced a decrease in tumor burden.