Compositions comprising anti-cd38 antibodies and lenalidomide

Abstract

Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and lenalidomide compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.

1 : A method of treating a cancer in a subject which comprises administering one or more anti-CD38 antibodies and one or more lenalidomide compounds to the subject, wherein malignant cells of the cancer express CD38. 
     
     
         2 - 3 . (canceled) 
     
     
         4 : The method of  claim 1 , wherein the cancer is a relapsed multiple myeloma or a refractory multiple myeloma. 
     
     
         5 : The method of  claim 1 , wherein the one or more lenalidomide compounds is lenalidomide. 
     
     
         6 : The method of  claim 1 , wherein the one or more anti-CD38 antibodies are administered in an effective amount, preferably a synergistic amount. 
     
     
         7 : The method of  claim 1 , wherein the one or more anti-CD38 antibodies and/or the one or more lenalidomide compounds are administered in a therapeutically effective amount. 
     
     
         8 : The method of  claim 1 , wherein at least one of the one or more anti-CD38 antibodies is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC). 
     
     
         9 . (canceled) 
     
     
         10 : The method of  claim 1 , wherein at least one of the one or more anti-CD38 antibodies is selected from the group consisting of:
 a) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 13, 15 and either SEQ ID NO: 14 or SEQ ID NO: 81, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 16, 17 and 18;   b) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 25, 26 and 27, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 28, 29 and 30;   c) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 1, 2 and 3, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 4, 5 and 6;   d) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 7, 8 and 9, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 10, 11 and 12;   e) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 19, 20 and 21, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 22, 23 and 24; and   f) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 31, 32 and 33, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 34, 35 and 36.   
     
     
         11 : The method of  claim 10 , wherein said antibody comprises a heavy chain having a V H  variable region represented by SEQ ID NO: 66, and a light chain having a V L  variable region represented by either SEQ ID NO: 62 or SEQ ID NO: 64. 
     
     
         12 : The method of  claim 10 , wherein said antibody comprises a heavy chain having a V H  variable region represented by SEQ ID NO: 72, and a light chain having a V L  variable region represented by either SEQ ID NO: 68 or SEQ ID NO: 70. 
     
     
         13 : The method of  claim 1 , wherein the one or more anti-CD38 antibodies are administered intravenously. 
     
     
         14 : The method of  claim 1 , wherein the one or more lenalidomide compounds are administered orally. 
     
     
         15 : The method of  claim 1 , wherein the one or more anti-CD38 antibodies and the one or more lenalidomide compounds are administered sequentially. 
     
     
         16 : The method of  claim 1 , and further comprising administering a dexamethasone compound, preferably dexamethasone, to the subject. 
     
     
         17 : The method of  claim 16 , wherein the dexamethasone compound is administered orally. 
     
     
         18 : The method of  claim 16 , wherein the dexamethasone compound is administered at a low dose. 
     
     
         19 : The method of  claim 16 , wherein the one or more anti-CD38 antibodies, the one or more lenalidomide compounds, and the dexamethasone compound are administered sequentially. 
     
     
         20 : The method of  claim 1 , and further comprising administering an anti-coagulation agent to the subject. 
     
     
         21 : The method of  claim 20 , wherein the anti-coagulation agent is selected from the group consisting of aspirin, warfarin, and low molecular weight heparin. 
     
     
         22 : The method of  claim 20 , wherein the one or more anti-CD38 antibodies, the one or more lenalidomide compounds, and the anti-coagulation agent are administered sequentially. 
     
     
         23 : A composition comprising
 a) at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and   b) at least one lenalidomide compound, preferably lenalidomide; and, optionally   c) a dexamethasone compound, preferably dexamethasone; and, optionally   d) an anti-coagulation agent.   
     
     
         24 : A kit comprising
 a) a first composition comprising at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38 +  cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and   b) a second composition comprising at least one lenalidomide compound, preferably lenalidomide.   
     
     
         25 - 28 . (canceled)