Immunoglobulin expression levels as biomarker for proteasome inhibitor response

Abstract

Methods of treating a tumor in a subject and methods of determining a treatment regimen for a subject with a tumor are provided herein. In exemplary aspects, the methods comprise measuring the level of expression of immunoglobulin, FCGR2B, a gene listed in Table 4, or a combination thereof. In exemplary aspects, the subject is a subject from which a sample was obtained, wherein the level of immunoglobulin, FCGR2B, a gene listed in Table 4, or a combination thereof, has been measured from the sample. Related kits, computer readable-storage media, systems, and methods implemented by a processor in a computer are further provided.

1 .- 20 . (canceled) 
     
     
         21 . A method of treating a tumor from which a sample was obtained, wherein the level of expression of (i) immunoglobulin (Ig), (ii) Fc gamma receptor 2B (FCGR2B), or (iii) both Ig and FCGR2B of the sample was greater than a reference level, the method comprising the step of administering an effective amount of a proteasome inhibitor. 
     
     
         22 . The method of  claim 21 , wherein the proteasome inhibitor is carfilzomib, bortezomib, disulfiram, and oprozomib. 
     
     
         23 . The method of  claim 22 , wherein the proteasome inhibitor is carfilzomib. 
     
     
         24 . The method of  claim 21 , wherein the tumor is a hematological tumor. 
     
     
         25 . The method of  claim 21 , wherein the tumor is in a subject and the subject has multiple myeloma, optionally, relapsed or refractory multiple myeloma. 
     
     
         26 . The method of  claim 25 , wherein the subject has newly diagnosed multiple myeloma. 
     
     
         27 . The method of  claim 25 , wherein the subject received one to three prior lines of therapy. 
     
     
         28 . The method of  claim 21 , wherein the sample comprised CD138-positive tumor cells and the level of expression of (i) immunoglobulin (Ig), (ii) Fc gamma receptor 2B (FCGR2B), or (iii) both Ig and FCGR2B of the sample was greater than a reference level. 
     
     
         29 . The method of  claim 21 , wherein the reference level is a cutoff correlative with a % specificity of at least 50% and a % sensitivity of at least 50%, as determined by a receiver operating characteristic (ROC) curve. 
     
     
         30 . The method of  claim 29 , wherein the ROC curve is based on (i) the distribution of Ig expression levels and/or FCGR2B expression levels of responders and (ii) the distribution of Ig expression levels and/or FCGR2B expression levels of non-responders. 
     
     
         31 . The method of  claim 21 , wherein the level of Ig expression and/or FCGR2B expression is at least 2-fold greater than the reference level. 
     
     
         32 . A method for treating a tumor in a subject, wherein the level of Ig expression and/or Fc gamma receptor 2B (FCGR2B) expression in the subject is greater than a reference level, said method comprising administering to the subject an effective amount of a proteasome inhibitor. 
     
     
         33 . A method for treating a tumor in a subject, said method comprising administering to the subject an effective amount of a proteasome inhibitor when the level of Ig expression and/or Fc gamma receptor 2B (FCGR2B) expression in the tumor is greater than a reference level. 
     
     
         34 . The method of  claim 33 , wherein:
 a. the proteasome inhibitor is carfilzomib, bortezomib, disulfiram, and oprozomib,   b. the tumor is a hematological tumor,   c. the tumor is in a subject and the subject has multiple myeloma, optionally, relapsed or refractory multiple myeloma, and/or   d. the tumor comprises CD138-positive tumor cells and the level of expression of (i) immunoglobulin (Ig), (ii) Fc gamma receptor 2B (FCGR2B), or (iii) both Ig and FCGR2B of the tumor cells is greater than a reference level.   
     
     
         35 . The method of  claim 34 , wherein the proteasome inhibitor is carfilzomib. 
     
     
         36 . The method of  claim 34 , wherein the subject has newly diagnosed multiple myeloma. 
     
     
         37 . The method of  claim 34 , wherein the subject received one to three prior lines of therapy. 
     
     
         38 . The method of  claim 33 , wherein the reference level is a cutoff correlative with a % specificity of at least 50% and a % sensitivity of at least 50%, as determined by a receiver operating characteristic (ROC) curve. 
     
     
         39 . The method of  claim 38 , wherein the ROC curve is based on (i) the distribution of Ig expression levels and/or FCGR2B expression levels of responders and (ii) the distribution of Ig expression levels and/or FCGR2B expression levels of non-responders. 
     
     
         40 . The method of  claim 33 , wherein the level of Ig expression and/or FCGR2B expression is at least 2-fold greater than the reference level.