METHODS OF USING ANTI-CD79b IMMUNOCONJUGATES

Abstract

Provided herein are methods of treating B-cell proliferative disorders in particular Follicular Lymphoma and/or Diffuse Large B-Cell Lymphoma using immunoconjugates comprising anti-CD79b antibodies in combination with additional therapeutic agents.

1 - 41 . (canceled) 
     
     
         42 . A method of treating a B-cell proliferative disorder in a human subject, comprising administering to the human subject (a) an immunoconjugate comprising the formula 
       
         
           
           
               
               
           
         
       
       and (b) an additional therapeutic agent,
 wherein Ab is an anti-CD79b antibody comprising (I) a hypervariable region-H1 (HVR-H1) comprising the amino acid sequence of SEQ ID NO: 21; (ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 22; (iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 23; (iv) a hypervariable region-L1 (HVR-L1) comprising the amino acid sequence of SEQ ID NO: 24; (v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 25; and (vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26, 
 wherein Val is valine, Cit is citrulline, p is between 1 and 8, and 
 wherein the immunoconjugate is administered to the human subject at a dose of about 1.8 mg/kg. 
 
     
     
         43 . The method of  claim 42 , wherein the anti-CD79b antibody comprises (i) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 19, and (ii) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 20. 
     
     
         44 . The method of  claim 42 , wherein the anti-CD79b antibody comprises:
 (i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 36 and a light chain comprising the amino acid sequence of SEQ ID NO: 35;   (ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 and a light chain comprising the amino acid sequence of SEQ ID NO: 35; or   (iii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 36 and a light chain comprising the amino acid sequence of SEQ ID NO: 38.   
     
     
         45 . The method of  claim 42 , wherein the anti-CD79b antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 36 and a light chain comprising the amino acid sequence of SEQ ID NO: 35. 
     
     
         46 . The method of  claim 42 , wherein the immunoconjugate is administered to the human subject at a dose of about 1.8 mg/kg once every three weeks. 
     
     
         47 . The method of  claim 42 , wherein the additional therapeutic agent comprises one or more chemotherapeutic agents selected from the group consisting of cyclophosphamide, doxorubicin, daunorubicin, vincristine, prednisone, and prednisolone. 
     
     
         48 . The method of  claim 42 , wherein the additional therapeutic agent comprises an anti-CD20 antibody. 
     
     
         49 . (canceled) 
     
     
         50 . The method of  claim 48 , wherein the anti-CD20 antibody is obinutuzumab. 
     
     
         51 . The method of  claim 50 , wherein obinutuzumab is administered to the human subject at a dose of about 1000 mg/m 2  once every three weeks. 
     
     
         52 . The method of  claim 48 , wherein the anti-CD20 antibody is rituximab. 
     
     
         53 . The method of  claim 52 , wherein rituximab is administered to the human subject at a dose of about 375 mg/m 2  once every three weeks. 
     
     
         54 . (canceled) 
     
     
         55 . The method of  claim 42 , wherein the B-cell proliferative disorder is cancer. 
     
     
         56 . The method of  claim 55 , wherein the cancer is selected from the group consisting of lymphoma, myeloma, non-Hodgkin's lymphoma (NHL), indolent NHL, aggressive NHL, relapsed aggressive NHL, relapsed indolent NHL, refractory NHL, refractory indolent NHL, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, leukemia, hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma. 
     
     
         57 . The method of  claim 55 , wherein the cancer is FL. 
     
     
         58 . The method of  claim 55 , wherein the cancer is DLBCL. 
     
     
         59 . The method of  claim 58 , wherein the anti-CD79b antibody comprises (i) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 19, and (ii) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 20. 
     
     
         60 . The method of  claim 58 , wherein the additional therapeutic agent comprises rituximab. 
     
     
         61 . The method of  claim 58 , wherein the additional therapeutic agent comprises obinutuzumab. 
     
     
         62 . The method of  claim 55 , wherein the cancer is relapsed or refractory FL (RR FL). 
     
     
         63 . The method of  claim 62 , wherein the anti-CD79b antibody comprises (i) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 19, and (ii) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 20. 
     
     
         64 . The method of  claim 62 , wherein the additional therapeutic agent comprises rituximab. 
     
     
         65 . The method of  claim 62 , wherein the additional therapeutic agent comprises obinutuzumab. 
     
     
         66 . The method of  claim 55 , wherein the cancer is relapsed or refractory DLBCL (RR DLBCL). 
     
     
         67 . The method of  claim 66 , wherein the anti-CD79b antibody comprises (i) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 19, and (ii) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 20. 
     
     
         68 . The method of  claim 66 , wherein the additional therapeutic agent comprises rituximab. 
     
     
         69 . The method of  claim 66 , wherein the additional therapeutic agent comprises obinutuzumab. 
     
     
         70 . A method of treating diffuse large-B cell lymphoma (DLBCL) in a human subject, comprising administering to the human subject (a) an immunoconjugate comprising the formula 
       
         
           
           
               
               
           
         
       
       and (b) an additional therapeutic agent,
 wherein Ab is an anti-CD79b antibody comprising a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 19, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 20, 
 wherein Val is valine, Cit is citrulline, p is between 1 and 8, 
 wherein the immunoconjugate is administered to the human subject at a dose of about 1.8 mg/kg; and 
 
       wherein the additional therapeutic agent comprises rituximab. 
     
     
         71 . A method of treating diffuse large-B cell lymphoma (DLBCL) in a human subject, comprising administering to the human subject (a) an immunoconjugate comprising the formula 
       
         
           
           
               
               
           
         
       
       and (b) an additional therapeutic agent,
 wherein Ab is an anti-CD79b antibody comprising a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 19, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 20, 
 wherein Val is valine, Cit is citrulline, p is between 1 and 8, 
 wherein the immunoconjugate is administered to the human subject at a dose of about 1.8 mg/kg; and 
 
       wherein the additional therapeutic agent comprises obinutuzumab. 
     
     
         72 . The method of  claim 70 , wherein the DLBCL is relapsed or refractory DLBCL (RR DLBCL). 
     
     
         73 . The method of  claim 71 , wherein the DLBCL is relapsed or refractory DLBCL (RR DLBCL).