Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, has achieved an overall response rate of 66%, as assessed by International Harmonization Project response criteria ( n=19/29: 95% CI, 46-82 ), in transplant-ineligible and failure patients with relapsed/refractory classical Hodgkin lymphoma ( cHL ) whose disease progressed on or after treatment with Brentuximab vedotin.
Complete remission was achieved in 21% of patients ( n=6/29 ) in the study. At the time of analysis, 89% of responses were ongoing ( n=17/19 ) with the median duration of response not yet reached ( range 1+ to 185+ days ).
These early findings, from the ongoing phase 1b KEYNOTE-013 study, were presented at the 56th American Society of Hematology ( ASH ) Annual Meeting in San Francisco.
Data from a cohort of the ongoing phase 1b KEYNOTE-013 study evaluated Pembrolizumab monotherapy at 10 mg/kg every two weeks in patients with relapsed / refractory classical Hodgkin lymphoma who had progressed on or after treatment with Brentuximab vedotin after failure of autologous stem-cell transplant, or who were transplant-ineligible ( n=29 ).
Adverse events were consistent with previously reported safety data for Pembrolizumab. The most common treatment-related adverse events ( occurring in greater than or equal to two patients ) included hypothyroidism ( n=3 ), pneumonitis ( n=3 ), constipation ( n=2 ), diarrhea ( n=2 ), nausea ( n=2 ), hypercholesterolemia ( n=2 ), hypertriglyceridemia ( n=2 ) and hematuria ( n=2 ).
Sixteen patients ( 55% ) experienced at least one treatment-related adverse event of any grade. Grade 3 treatment-related adverse events occurred in a total of three patients and included axillary pain, hypoxia, joint swelling, and pneumonitis.
No grade 4 treatment-related adverse events or treatment-related deaths were reported.
KEYNOTE-013 is an ongoing multi-center, non-randomized trial of approximately 106 patients evaluating the safety, tolerability, and efficacy of Pembrolizumab monotherapy in patients with blood cancers, including myelodysplastic syndromes, multiple myeloma, Hodgkin lymphoma, mediastinal large B cell lymphoma and non-Hodgkin’s lymphoma.
The primary endpoints of the study include overall safety, tolerability, and complete remission rate ( as measured by International Harmonization Project Response Criteria ); secondary endpoints include overall response rate ( ORR ), progression-free survival ( PFS ), overall survival ( OS ) and duration of response.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Pembrolizumab releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. ( Xagena )
Source: Merck, 2014