Treatment of hodgkin lymphoma using an anti-pd-1 antibody

Abstract

This disclosure provides to methods for treating Hodgkin lymphoma in a subject comprising administering to the subject an anti-Programmed Death-1 (PD-1) antibody to a subject, wherein the subject has received at least one prior treatment for Hodgkin lymphoma.

1 . A method of treating a subject afflicted with a tumor derived from a Hodgkin lymphoma, comprising administering to the subject an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 receptor (PD-1) (“anti-PD-1 antibody”), wherein the subject was not responsive to a prior treatment comprising (i) an autologous stem cell therapy, and (ii) brentuximab vedotin. 
     
     
         2 . The method of  claim 1 , wherein (i) the subject failed to achieve a partial response after the prior treatment, (ii) the subject had a relapse after a complete response after the prior treatment, and/or (iii) the subject had progressive disease after a partial response or stable disease after the prior treatment. 
     
     
         3 . The method of  claim 1 , further comprising administering doxorubicin, vinblastine, and dacarbazine to the subject. 
     
     
         4 . The method of  claim 1 , wherein the subject is not administered bleomycin. 
     
     
         5 . The method of  claim 3 , wherein the doxorubicin, vinblastine, and dacarbazine are administered once about every one, two, three, or four weeks. 
     
     
         6 . The method of  claim 3 , wherein the doxorubicin is administered at a dose of about 10 mg/m 2  to about 40 mg/m 2 ; the vinblastine is administered at a dose of about 0.1 mg/m 2  to about 10 mg/m 2 ; and/or the dacarbazine is administered at a dose of about 200 mg/m 2  to about 500 mg/m 2 . 
     
     
         7 . The method of  claim 3 , wherein the doxorubicin is administered at a dose of 25 mg/m 2 , the vinblastine is administered at a dose of 6 mg/m 2 , and the dacarbazine is administered at a dose of 375 mg/m 2  once about every 2 weeks. 
     
     
         8 . The method of  claim 1 , wherein the anti-PD-1 antibody is nivolumab. 
     
     
         9 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered at ci) a dose ranging from about 0.1 mg/kg to about 10.0 mg/kg body weight once about every 1, 2, or 3 weeks; or (ii) a flat dose of about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 320 mg, about 340 mg, about 360 mg, about 380 mg, about 400 mg, about 420 mg, about 440 mg, about 460 mg, about 480 mg, about 500 mg, or about 550 mg, about once every 1, 2, 3 or 4 weeks. 
     
     
         10 . The method of  claim 1 , wherein the Hodgkin lymphoma has a genetic alteration at 9p24.1. 
     
     
         11 . The method of  claim 1 , wherein the Hodgkin lymphoma expresses PD-L1 and/or PD-L2. 
     
     
         12 . The method of  claim 11 , wherein the PD-L1 and/or PD-L2 expression is at least about 1%. 
     
     
         13 . The method of  claim 1 , wherein the subject exhibits progression-free survival of at least about one month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about one year, at least about eighteen months, at least about two years, at least about three years, at least about four years, or at least about five years after the initial administration. 
     
     
         14 . The method of  claim 1 , wherein the subject exhibits an overall survival of at least about one month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about one year, at least about eighteen months, at least about two years, at least about three years, at least about four years, or at least about five years after the initial administration. 
     
     
         15 . A kit comprising:
 (a) an anti-PD-1 antibody; and   (b) instructions for using the anti-PD-1 antibody in the method of  claim 1 .   
     
     
         16 . The method of  claim 1 , wherein the anti-PD-1 antibody is pembrolizumab. 
     
     
         17 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered at a dose of about 3 mg/kg body weight once about every 2 weeks. 
     
     
         18 . The method of  claim 8 , wherein the anti-PD-1 antibody is administered at a flat dose of about 240 mg once every 2 weeks. 
     
     
         19 . The method of  claim 8 , wherein the anti-PD-1 antibody is administered at a flat dose of about 480 mg once every 4 weeks. 
     
     
         20 . The method of  claim 16 , wherein the anti-PD-1 antibody is administered at a flat dose of about 200 mg once every 3 weeks.