Methods of Treating High Risk Multiple Myeloma

Abstract

Disclosed are methods of treating a subject having high-risk multiple myeloma, methods of achieving negative minimal residual disease status in a subject having multiple myeloma, and methods of predicting a likelihood of, or decreasing a risk of, relapse and/or disease progression in a subject having multiple myeloma.

What is claimed is: 
     
         1 . A method of achieving a negative minimal residual disease status in a subject having high-risk multiple myeloma, comprising administering to the subject an anti-CD38 antibody, lenalidomide, and dexamethasone for a time sufficient to achieve the negative minimal residual disease status, wherein the anti-CD38 antibody comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2, a HCDR3, a light chain complementarity determining region (LCDR) 1, a LCDR2 and a LCDR3 amino acid sequences of SEQ ID NOs: 6, 7, 8, 9, 10 and 11, respectively. 
     
     
         2 . The method of  claim 1 , wherein the subject has one or more chromosomal abnormalities comprising:
 a) t(4;14)(p16;q32);   b) t(14;16)(q32;q23);   c) del17p;   d) t(4;14)(p16;q32) and t(14;16)(q32;q23);   e) t(4;14)(p16;q32) and del17p;   f) t(14;16)(q32;q23) and del17p; or   g) t(4;14)(p16;q32), t(14;16)(q32;q23) and del17p.   
     
     
         3 . The method of  claim 1 , wherein the subject has relapsed or refractory multiple myeloma. 
     
     
         4 . The method of  claim 1 , wherein the anti-CD38 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 5. 
     
     
         5 . The method of  claim 1 , wherein the anti-CD38 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 12 and a light chain comprising the amino acid sequence of SEQ ID NO: 13. 
     
     
         6 . The method of  claim 1 , wherein
 a) the anti-CD38 antibody is administered as an intravenous infusion at a dose of about 16 mg/kg once per week in a 28-day cycle on days 1, 8, 15, and 22 for cycles 1 and 2, once every 2 weeks in a 28-day cycle on days 1 and 15 during cycles 3 through 6, and once every 4 weeks thereafter;   b) lenalidomide is administered at a dose of between about 10 mg to about 25 mg orally in a 28-day cycle on days 1 to 21; and   c) dexamethasone is administered at a dose of between about 20 mg to about 40 mg weekly.   
     
     
         7 . The method of  claim 1 , wherein the negative minimal residual disease status:
 a) is detected by evaluating an amount of myeloma cells in a bone marrow aspirate sample from the subject;   b) is determined at a sensitivity of 0.01%, 0.001%, 0.0001%, or a combination thereof,   or both a) and b).   
     
     
         8 . A method of decreasing a risk of relapse and/or disease progression in a subject having high-risk multiple myeloma, comprising administering to the subject a therapeutically effective amount of an anti-CD38 antibody, lenalidomide, and dexamethasone to achieve a negative minimal residual disease status, wherein the negative residual disease status is indicative of a decreased risk of relapse and/or disease progression, and wherein the anti-CD38 antibody comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2, a HCDR3, a light chain complementarity determining region (LCDR) 1, a LCDR2 and a LCDR3 amino acid sequences of SEQ ID NOs: 6, 7, 8, 9, 10 and 11, respectively. 
     
     
         9 . The method of  claim 8 , wherein the subject has one or more chromosomal abnormalities comprising:
 a) t(4;14)(p16;q32);   b) t(14;16)(q32;q23);   c) del17p;   d) t(4;14)(p16;q32) and t(14;16)(q32;q23);   e) t(4;14)(p16;q32) and del17p;   f) t(14;16)(q32;q23) and del17p; or   g) t(4;14)(p16;q32), t(14;16)(q32;q23) and del17p.   
     
     
         10 . The method of  claim 8 , wherein the subject has relapsed or refractory multiple myeloma. 
     
     
         11 . The method of  claim 8 , wherein the anti-CD38 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 5. 
     
     
         12 . The method of  claim 8 , wherein the anti-CD38 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 12 and a light chain comprising the amino acid sequence of SEQ ID NO: 13. 
     
     
         13 . The method of  claim 8 , wherein
 a) the anti-CD38 antibody is administered as an intravenous infusion at a dose of about 16 mg/kg once per week in a 28-day cycle on days 1, 8, 15, and 22 for cycles 1 and 2, once every 2 weeks in a 28-day cycle on days 1 and 15 during cycles 3 through 6, and once every 4 weeks thereafter;   b) lenalidomide is administered at a dose of between about 10 mg to about 25 mg orally in a 28-day cycle on days 1 to 21; and   c) dexamethasone is administered at a dose of between about 20 mg to about 40 mg weekly.   
     
     
         14 . The method of  claim 8 , wherein the negative minimal residual disease status:
 a) is detected by evaluating an amount of myeloma cells in a bone marrow aspirate sample from the subject;   b) is determined at a sensitivity of 0.01%, 0.001%, 0.0001%, or a combination thereof,   or both a) and b).   
     
     
         15 . A method of treating a subject having high-risk multiple myeloma, comprising administering to the subject a therapeutically effective amount of an anti-CD38 antibody, lenalidomide, and dexamethasone for a time sufficient to treat the high-risk multiple myeloma, wherein the anti-CD38 antibody comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2, a HCDR3, a light chain complementarity determining region (LCDR) 1, a LCDR2 and a LCDR3 amino acid sequences of SEQ ID NOs: 6, 7, 8, 9, 10 and 11, respectively. 
     
     
         16 . The method of  claim 15 , wherein the subject has one or more chromosomal abnormalities comprising:
 a) t(4;14)(p16;q32);   b) t(14;16)(q32;q23);   c) del17p;   d) t(4;14)(p16;q32) and t(14;16)(q32;q23);   e) t(4;14)(p16;q32) and del17p;   f) t(14;16)(q32;q23) and del17p; or   g) t(4;14)(p16;q32), t(14;16)(q32;q23) and del17p.   
     
     
         17 . The method of  claim 15 , wherein the subject has relapsed or refractory multiple myeloma. 
     
     
         18 . The method of  claim 15 , wherein the anti-CD38 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 5. 
     
     
         19 . The method of  claim 15 , wherein the anti-CD38 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 12 and a light chain comprising the amino acid sequence of SEQ ID NO: 13. 
     
     
         20 . The method of  claim 15 , wherein
 a) the anti-CD38 antibody is administered as an intravenous infusion at a dose of about 16 mg/kg once per week in a 28-day cycle on days 1, 8, 15, and 22 for cycles 1 and 2, once every 2 weeks in a 28-day cycle on days 1 and 15 during cycles 3 through 6, and once every 4 weeks thereafter;   b) lenalidomide is administered at a dose of between about 10 mg to about 25 mg orally in a 28-day cycle on days 1 to 21; and   c) dexamethasone is administered at a dose of between about 20 mg to about 40 mg weekly.   
     
     
         21 . The method of  claim 15 , wherein the method achieves a negative minimal residual disease status in the subject. 
     
     
         22 . The method of  claim 21 , wherein the negative minimal residual disease status:
 a) is detected by evaluating an amount of myeloma cells in a bone marrow aspirate sample from the subject;   b) is determined at a sensitivity of 0.01%, 0.001%, 0.0001%, or a combination thereof,   or both a) and b).