Pembrolizumab Active in Relapsed Classical Hodgkin Lymphoma

Treatment with the anti–PD-1 antibody pembrolizumab was safe and active in a small study of patients with relapsed or refractory classical Hodgkin lymphoma whose disease progressed after treatment with brentuximab vedotin. Ninety percent of patients in the study had some evidence of tumor shrinkage on treatment.

“The high response rate to PD-1 blockade seen in this study supports the hypothesis that classic Hodgkin lymphoma is highly dependent on the PD-1 pathway for survival,” wrote researchers led by Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute in Boston. “The genetically defined sensitivity to PD-1 blockade in Hodgkin lymphoma distinguishes this tumor from most other solid and hematologic malignancies, and could explain why the therapeutic response to PD-1 blockade in Hodgkin lymphoma is higher than in any other tumor type studied to date.”

Based on the known frequency of genetic alterations in Hodgkin lymphoma, it was included as an independent cohort in the KEYNOTE-013 trial. The results were published in the Journal of Clinical Oncology.

Thirty-one patients with relapsed or refractory Hodgkin lymphoma were enrolled and treated with pembrolizumab 10 mg/kg every 2 weeks until disease progression. This was a heavily pretreated patient population with 55% of patients having had four or more prior lines of therapy and 71% of patients having relapsed after autologous stem cell transplantation (ASCT).

After treatment, five of 31 patients achieved a complete response (16%). An additional 15 patients (45%) achieved partial response. The overall response rate was 65%. Twenty-eight of the 31 patients (90%) had some sort of decrease in tumor burden.

The researchers noted that the complete response rate (CRR) was lower than they anticipated.

“In fact, the primary hypothesis of the study was not met because the lower bound of the 90% CI for CRR did not exclude the 10% null hypothesis,” the researchers wrote. “Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies.”

Of the 20 patients who responded to pembrolizumab, 70% of them had a duration of response of 24 weeks or longer at a median follow-up of about 18 months. The majority of best responses occurred at the first assessment at 12 weeks. The progression-free survival at 24 weeks was 69%, and at 52 weeks it was 46%.

“In the present work, the response rate of pembrolizumab appeared lower in transplantation-naive patients, who composed 30% of the evaluable patients compared with patients who relapsed after ASCT (44% vs 73%),” the researchers wrote. “This is consistent with prior studies documenting, in general, a lower response rate and worse prognosis for patients ineligible for ASCT because of lack of response to standard-dose salvage regimens.”

The most common adverse events were hypothyroidism, diarrhea, nausea, and pneumonitis. Grade 3 drug-related adverse events occurred in 16% of patients. No grade 4 events or deaths related to the treatment occurred.

“Our results also suggest that treatment with pembrolizumab promotes expansion of T-cell and NK-cell populations in the peripheral blood and upregulates IFN-Æ´–activated pathways, suggesting that modulation of the PD-1/PD-L1 axis activates T-cell/IFN-Æ´ signaling pathways,” the researchers wrote.