Craig H. Moskowitz, MD
Treatment with the PD-1 inhibitor pembrolizumab (Keytruda) generated responses in 66% of patients with heavily pretreated classical Hodgkin lymphoma (cHL), according to preliminary results of a phase IB study reported at the 56th Annual Meeting of the American Society of Hematology (ASH).1
Of the 29 evaluable patients with cHL who received pembrolizumab, six patients (21%) experienced complete remission while 13 patients (45%) achieved a partial remission, lead investigator Craig H. Moskowitz, MD, said during a press briefing as the meeting opened Saturday. Among the remaining participants, six patients (21%) had stable disease while four individuals (14%) experienced progressive disease.
The patients who participated in the trial had been heavily pretreated, having received a median of four prior therapies. In total, 69% of the patients (n = 20) had relapsed following stem cell transplant and, by trial design, all patients had failed treatment with 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, who is clinical director in the Division of Hematologic Oncology and Steven A. Greenberg Chair 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.2
Moskowitz said the activity that pembrolizumab 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, pembrolizumab became the first PD-1 inhibitor to hit the market in the United States when the FDA approved the agent for the treatment of patients with unresectable or metastatic melanoma whose disease has progressed after prior therapies. Merck, which is developing the drug, is studying the agent in more than 30 types of cancers, including bladder, non–small cell lung, and head and neck.
Pembrolizumab is a monoclonal antibody that stimulates an antitumor 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.
In their conference abstract, Moskowitz and colleagues said cHL “may represent a uniquely vulnerable target for PD-1 blockade therapy” because of genetic characteristics that result in overexpression of PD-1 ligands.
Among enrolled patients, PD-L1 expression was observed in 100% of the evaluable samples, Moskowitz said.
During the trial, patients were treated with pembrolizumab alone at 10 mg/kg intravenously every 2 weeks until progression, excessive toxicity, or completion of 2 years of treatment. Primary endpoints of the trial focused on safety, tolerability, and complete remission. Response assessment was conducted at week 12 and every 8 weeks thereafter. Results were reported from the time of analysis in November.
In addition to 20 patients who had failed 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% (n = 19); among those who had previously failed transplant, the ORR reached 75% and four of these patients achieved a complete remission.
Pembrolizumab was extremely well tolerated, Moskowitz said. The most commonly reported adverse events were grade 1-2 respiratory events (20%) and thyroid disorders (20%).
“I think the safety profile of these drugs are really quite good—very little grade 3/4 toxicity,” Moskowitz said.
No grade 4 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% of patients had ongoing responses (n = 17). While four patients experienced disease progression, all four experienced a decrease in tumor burden.
Moskowitz CH, Ribrag V, Michot JM, et al. PD-1 blockade with the monoclonal antibody pembrolizumab (MK-3475) in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study (KEYNOTE-013). Presented at: 56th Annual Meeting of the American Society of Hematology; December 5-9, 2014; San Francisco, California. Abstract 290.
NIH Clinical Trials Registry. www.ClinicalTrials.gov website. ID Number: NCT01953692.
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