Use of anti-cd19 maytansinoid immunoconjugate antibody for the treatment of b-cell malignancies symptoms

Abstract

An anti-CD19 maytansinoid immunoconjugate is used for treating B-cell malignancies symptom, in particular Non-Hodgkin's lymphoma.

1 .- 44 . (canceled) 
     
     
         45 . A method of treating Non-Hodgkin's lymphoma (NHL) in a human patient in need thereof, said method comprising:
 a) administering to said patient an initial dose of 55 mg/m 2  of an anti-CD19 maytansinoid immunoconjugate, and   b) administering to said patient a plurality of subsequent doses of 55 mg/m 2  of the anti-CD19 maytansinoid immunoconjugate,   wherein said anti-CD19 maytansinoid immunoconjugate comprises an antibody conjugated to the maytansinoid DM4 through a N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) linker,   wherein the antibody specifically binds to a CD19 antigen and comprises a light chain and a heavy chain, wherein the sequence of said light chain has at least 85% identity with SEQ ID NO: 7; and the sequence of said heavy chain has at least 85% identity with SEQ ID NO: 8.   
     
     
         46 . The method according to  claim 45 , wherein the antibody is huB4 antibody comprising a light chain having the sequence of SEQ ID NO: 7 and a heavy chain having the sequence of SEQ ID NO: 8. 
     
     
         47 . The method according to  claim 45 , wherein said NHL is Diffuse Large B-cell lymphoma (DLBCL), a follicular lymphoma (FL), a Mantle cell lymphoma (MCL), a Marginal zone lymphoma (MZL), a Small lymphocytic lymphoma (SLL), or a Waldenström macroglobulinemia (WM). 
     
     
         48 . The method according to  claim 47 , wherein said NHL is Diffuse Large B-cell lymphoma (DLBCL). 
     
     
         49 . The method according to  claim 45 , wherein said NHL is a relapsed or refractory NHL. 
     
     
         50 . The method according to  claim 45 , wherein said NHL is a NHL expressing CD19. 
     
     
         51 . The method according to  claim 45 , wherein said patient has already been treated for the NHL. 
     
     
         52 . The method according to  claim 45 , wherein said patient has failed rituximab therapy. 
     
     
         53 . The method according to  claim 45 , wherein said NHL is rituximab resistant. 
     
     
         54 . The method according to  claim 45 , wherein said patient has received an autologous or allogeneic stem cell transplant. 
     
     
         55 . The method according to  claim 45 , wherein the anti-CD19 maytansinoid immunoconjugate is administered intravenously. 
     
     
         56 . The method according to  claim 45 , wherein said method comprises:
 a) administering to said patient an initial dose of 55 mg/m 2  of the anti-CD19 maytansinoid immunoconjugate,   b) administering to the patient at least 3 subsequent doses of 55 mg/m 2  of the anti-CD19 maytansinoid immunoconjugate separated in time from each other by about one week, and   c) administering to the patient at least 3 further subsequent doses of 55 mg/m 2  of the anti-CD19 maytansinoid immunoconjugate separated in time from each other by about two weeks.   
     
     
         57 . The method according to  claim 46 , wherein 3.5 molecules of DM4 are bound through the SPDB linker to each huB4 antibody molecule. 
     
     
         58 . A method of treating Non-Hodgkin's lymphoma (NHL) in a human patient in need thereof, wherein the method comprises:
 administering to the patient 4 doses of 55 mg/m 2  of an anti-CD19 maytansinoid immunoconjugate separated in time from each other by one week, and administering to the patient 4 subsequent doses of 55 mg/m 2  of the anti-CD19 maytansinoid immunoconjugate separated in time from each other by two weeks,   wherein said anti-CD19 maytansinoid immunoconjugate comprises an antibody conjugated to the maytansinoid DM4 through a N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) linker; and the antibody comprises a light chain and a heavy chain, wherein the sequence of said light chain has at least 85% identity with SEQ ID NO: 7; and the sequence of said heavy chain has at least 85% identity with SEQ ID NO: 8.   
     
     
         59 . The method according to  claim 58 , wherein the antibody is huB4 antibody comprising a light chain having the sequence of SEQ ID NO: 7 and a heavy chain having the sequence of SEQ ID NO: 8. 
     
     
         60 . The method according to  claim 58 , wherein said NHL is Diffuse Large B-cell lymphoma (DLBCL), a follicular lymphoma (FL), a Mantle cell lymphoma (MCL), a Marginal zone lymphoma (MZL), a Small lymphocytic lymphoma (SLL), or a Waldenström macroglobulinemia (WM). 
     
     
         61 . The method according to  claim 60 , wherein said NHL is Diffuse Large B-cell lymphoma (DLBCL).