Methods for treating lymphomas in certain patient populations and screening patients for said therapy

Abstract

Methods for predicting a response of a patient having a lymphoma to a therapy regimen of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione using prognostic factors of a patient's disease burden, absolute lymphocyte count or time since last rituximab therapy are disclosed. Specific methods of treating a lymphoma encompass the administration of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione to a patient who has one or more of the favorable profiles, alone or in combination with immunosuppressive agents such as rituximab.

What is claimed is: 
     
         1 . A method for treating a lymphoma in a patient, which comprises administering 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione to a patient having one or more of the following:
 a) a disease burden of less than 50 cm 2 ;   b) an absolute lymphocyte count greater than 0.6×10 9 /L; or   c) not less than 230 days since last rituximab therapy.   
     
     
         2 . A method for treating a lymphoma in a patient, comprising:
 a) determining the patient's disease burden, an absolute lymphocyte count or time since last rituximab therapy;   b) predicting a response of the patient to a regimen of 3 (4 amino 1 oxo 1,3 dihydro isoindol 2 yl)piperidine 2,6 dione in a therapy for a lymphoma by comparing values in a) to values of a disease burden of 50 cm 2 , an absolute lymphocyte count of 0.6×10 9 /L, or 230 days since last rituximab therapy; and   c) administering a therapeutically effective amount of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione to the patient who has a disease burden of less than 50 cm 2 , an absolute lymphocyte count greater than 0.6×10 9 /L, or not less than 230 days since last rituximab therapy.   
     
     
         3 . The method of  claim 1 , wherein the patient has two or more of the following: a disease burden of less than 50 cm 2 , an absolute lymphocyte count greater than 0.6×10 9 /L, or not less than 230 days since last rituximab therapy. 
     
     
         4 . The method of  claim 1 , wherein the patient has all of the following: a disease burden of less than 50 cm 2 , an absolute lymphocyte count greater than 0.6×10 9 /L, and not less than 230 days since last rituximab therapy. 
     
     
         5 . The method of  claim 1 , wherein the patient is refractory to rituximab. 
     
     
         6 . The method of  claim 1 , wherein the patient has not been treated with rituximab. 
     
     
         7 . The method of  claim 1 , wherein the lymphoma is relapsed, refractory or resistant to conventional therapy. 
     
     
         8 . The method of  claim 1 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         9 . The method of  claim 1 , wherein the lymphoma is mantle cell lymphoma, follicular center lymphoma, diffuse large B-cell lymphoma, transformed lymphoma, lymphocytic lymphoma of intermediate differentiation, intermediate lymphocytic lymphoma, diffuse poorly differentiated lymphocytic lymphoma, centrocytic lymphoma, diffuse small-cleaved cell lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, or mantle zone lymphoma. 
     
     
         10 . The method of  claim 1 , wherein the amount of 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is about 10, 15, 20 or 25 mg per day. 
     
     
         11 . The method of  claim 1 , wherein the amount of 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is about 25 mg per day. 
     
     
         12 . The method of  claim 1 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is enantiomerically pure. 
     
     
         13 . The method of  claim 12 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is S enantiomer. 
     
     
         14 . The method of  claim 12 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is R enantiomer. 
     
     
         15 . The method of  claim 1 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered orally. 
     
     
         16 . The method of  claim 15 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in the form of a capsule. 
     
     
         17 . The method of  claim 16 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in the form of a capsule of 5 mg, 10 mg, 15 mg or 25 mg. 
     
     
         18 . The method of  claim 1 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered for 21 days followed by seven days rest in a 28 day cycle. 
     
     
         19 . The method of  claim 18 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in an amount of about 25 mg per day for 21 days followed by seven days rest in a 28 day cycle. 
     
     
         20 . The method of  claim 19 , further comprising administration of the compound for 52 weeks as tolerated or until disease progression. 
     
     
         21 . The method of  claim 20 , further comprising administering the compound to a patient who achieves a complete response for two additional cycles. 
     
     
         22 . The method of  claim 1 , further comprising administering a therapeutically effective amount of a second active agent. 
     
     
         23 . The method of  claim 22 , wherein the second active agent is an antibody, a hematopoietic growth factor, a cytokine, an anti-cancer agent, an antibiotic, a cox-2 inhibitor, an immunomodulatory agent, an immunosuppressive agent, or a corticosteroid. 
     
     
         24 . The method of  claim 1 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered before administering rituximab. 
     
     
         25 . The method of  claim 1 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered before administering immune suppressive agents. 
     
     
         26 . The method of  claim 1 , wherein the disease burden is estimated by no single tumor with diameter greater than 4.5 cm. 
     
     
         27 . The method of  claim 2 , wherein the patient has two or more of the following: a disease burden of less than 50 cm 2 , an absolute lymphocyte count greater than 0.6×10 9 /L, or not less than 230 days since last rituximab therapy. 
     
     
         28 . The method of  claim 2 , wherein the patient has all of the following: a disease burden of less than 50 cm 2 , an absolute lymphocyte count greater than 0.6×10 9 /L, and not less than 230 days since last rituximab therapy. 
     
     
         29 . The method of  claim 2 , wherein the patient is refractory to rituximab. 
     
     
         30 . The method of  claim 2 , wherein the patient has not been treated with rituximab. 
     
     
         31 . The method of  claim 2 , wherein the lymphoma is relapsed, refractory or resistant to conventional therapy. 
     
     
         32 . The method of  claim 2 , wherein the lymphoma is non-Hodgkin's lymphoma. 
     
     
         33 . The method of  claim 2 , wherein the lymphoma is mantle cell lymphoma, follicular center lymphoma, diffuse large B-cell lymphoma, transformed lymphoma, lymphocytic lymphoma of intermediate differentiation, intermediate lymphocytic lymphoma, diffuse poorly differentiated lymphocytic lymphoma, centrocytic lymphoma, diffuse small-cleaved cell lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, or mantle zone lymphoma. 
     
     
         34 . The method of  claim 2 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered before administering rituximab. 
     
     
         35 . The method of  claim 2 , wherein 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered before administering immune suppressive agents. 
     
     
         36 . The method of  claim 2 , wherein the disease burden is estimated by no single tumor with diameter greater than 4.5 cm.