Positive results from a cohort of patients in its ongoing phase 1b trial ( CheckMate-039 ) which evaluated PD-1 immune checkpoint inhibitor, Nivolumab ( Opdivo), in patients with relapsed or refractory hematological malignancies ( n=23 ).
Results showed high levels of response in patients with relapsed or refractory classical Hodgkin lymphoma ( HL ), with an overall response rate of 87% ( n=20 ) and stable disease in 13% ( n=3 ), were published in The New England Journal of Medicine ( NEJM ) and presented during the 56th annual meeting of the American Society for Hematology.
In patients with Hodgkin Lymphoma, initial treatment typically consists of chemotherapy and/or radiation therapy, followed by an autologous stem cell transplant ( ASCT ) if the disease recurs. For those who relapse within one year after receiving a standard of care like ASCT, the median survival is only 1.3 years after progression.
CheckMate-039 is an ongoing phase 1 dose escalation study of patients with relapsed and refractory hematological malignancies, which includes a cohort evaluating Nivolumab in patients with Hodgkin lymphoma after failure of autologous stem cell transplant and Brentuximab.
The cohort includes 23 patients who were treated with Nivolumab 3 mg/kg at week one, week four and every two weeks until disease progression or complete response or for a maximum of two years.
The primary endpoints included evaluating the safety and tolerability of Nivolumab. Secondary endpoints included determining antitumor activity, characterizing Nivolumab pharmacokinetics and immunogenicity, and assessing PD-L1 and PD-L2 expression as a predictive biomarker.
In the trial, 87% ( n=20 ) achieved an overall response, with 17% ( n=4 ) achieving complete response and 70% ( n=16 ) a partial response.
The remaining patients, 13% ( n=3 ), experienced stable disease. Of the patients who achieved a complete and partial response, 60% ( n=12 ) had their first response within eight weeks ( range: 3-39 weeks ).
Data from the study also showed a progression-free survival rate of 86% at 24 weeks, meaning patients lived six months longer without their disease worsening.
Safety results were reported in all patients treated in the study. Overall, drug-related adverse events of any grade were reported in 78% of patients ( n=18 ), with the most common being rash ( 22% ) and decreased platelet count ( 17% ). Of these, grade 3 adverse events occurred in 22% of patients ( n=5 ).
There were no treatment-related grade 4 or 5 adverse events.
Nivolumab is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 ( programmed death-1 ) expressed on activated T-cells.
Hodgkin lymphoma is a cancer of the lymphatic system, which originates in the white blood cells. Hodgkin lymphoma is one of two main types of lymphomas.
The five-year survival rate for advanced Hodgkin lymphoma is approximately 65% in the U.S.
The median age of diagnosis is 38 in the U.S. This year, more than 9,100 new cases are estimated to be diagnosed with more than 1,100 deaths expected. ( Xagena )
Source: BMS, 2014