Combinations and uses thereof
The present disclosure describes a pharmaceutical combination of an anti-CD19 antibody and a phosphoinositide 3-kinase inhibitor for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and/or acute lymphoblastic leukemia.
1. A method for treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and/or acute lymphoblastic leukemia in a patient in need thereof, said method comprising administering to the patient an antibody specific for CD19,
wherein said antibody comprises an HCDR1 region of sequence SYVMH (SEQ ID NO: 1), an HCDR2 region of sequence NPYNDG (SEQ ID NO: 2), an HCDR3 region of sequence GTYYYGTRVFDY (SEQ ID NO: 3), an LCDR1 region of sequence RSSKSLQNVNGNTYLY (SEQ ID NO: 4), an LCDR2 region of sequence RMSNLNS (SEQ ID NO: 5), and an LCDR3 region of sequence MQHLEYPIT (SEQ ID NO: 6), a heavy chain constant domain of the sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVV HQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY PSDIAVEWESNGQENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGK (SEQ ID NO: 12), and a light chain constant domain of the sequence RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 13), and idelalisib.
2. The method of claim 1 , wherein said antibody specific for CD19 and idelalisib are administered separately.
3. The method of claim 2 , wherein said antibody specific for CD19 and idelalisib are administered separately physically.
4. The method of claim 2 , wherein said antibody specific for CD19 and idelalisib are administered separately in time.
5. The method of claim 1 , wherein said antibody specific for CD19 and idelalisib are administered together.
6. The method of claim 1 , wherein idelalisib is administered prior to administration of the antibody specific for CD19.
7. The method of claim 1 , wherein idelalisib is administered after administration of the antibody specific for CD19.
8. The method of claim 1 wherein the antibody specific for CD19 comprises a variable heavy chain of the sequence EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGYINPY NDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWG QGTLVTVSS (SEQ ID NO: 10) and a variable light chain of the sequence DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYR MSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIK (SEQ ID NO: 11).
9. The method of claim 1 , wherein the patient has non-Hodgkin's lymphoma.
10. The method of claim 9 , wherein the non-Hodgkin's lymphoma is follicular lymphoma.
11. The method of claim 9 , wherein the non-Hodgkin's lymphoma is small lymphocytic lymphoma.
12. The method of claim 9 , wherein the non-Hodgkin's lymphoma is mucosa-associated lymphoid tissue lymphoma.
13. The method of claim 9 , wherein the non-Hodgkin's lymphoma is marginal zone lymphoma.
14. The method of claim 9 , wherein the non-Hodgkin's lymphoma is diffuse large B cell lymphoma.
15. The method of claim 9 , wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma.
16. The method of claim 9 , wherein the non-Hodgkin's lymphoma is mantle cell lymphoma.
17. The method of claim 1 , wherein the patient has chronic lymphocytic leukemia.
18. The method of claim 1 , wherein the patient has acute lymphoblastic leukemia.