ANTI-CD19 THERAPY IN COMBINATION WITH LENALIDOMIDE FOR THE TREATMENT OF LEUKEMIA OR LYMPHOMA
The present disclosure is directed to a therapeutic combination of an anti-CD19 antibody and lenalidomide for use in the treatment of hematological cancer patients. Furthermore, the present disclosure concerns extending the overall survival and/or the progression free survival in patients having specific types of hematological cancer.
1 : A method for extending overall survival and/or the progression free survival of hematological cancer patients, said method comprising administering to said patients a therapeutic combination of an anti-CD19 antibody and lenalidomide.
2 - 3 . (canceled)
4 : The method of claim 1 wherein said hematological cancer patients have received one line of previous treatment and wherein the 12-months overall survival rate is 80% or more.
5 : The method of claim 1 wherein the 12-months progression free survival is 55% or more.
6 : The method of claim 1 wherein said hematological cancer patients have received two or more lines of previous treatment and wherein the 12-months overall survival rate is 55% or more.
7 : The method of claim 6 wherein the 12-months progression free survival is 35% or more.
8 : The method of claim 1 wherein said hematological cancer patients have non-Hodgkin's lymphoma selected from the group of follicular lymphoma, small lymphocytic lymphoma, mucosa-associated lymphoid tissue, marginal zone lymphoma, diffuse large B cell lymphoma, Burkitt's lymphoma and mantle cell lymphoma.
9 : The method of claim 1 wherein said hematological cancer patients have a germinal center B-cell type (GCB) DLBCL and wherein the 12-months overall survival rate is 60% or more.
10 : The method of claim 9 wherein the 12-months progression free survival is 35% or more.
11 : The method of claim 1 wherein said hematological cancer patients have a non-germinal center B-cell type (non-GCB) DLBCL and wherein the 12-months overall survival rate is 80% or more.
12 : The method of claim 11 wherein the 12-months progression free survival is 70% or more.
13 : The method of claim 1 wherein said anti-CD19 antibody comprises an HCDR1 region comprising the sequence SYVMH (SEQ ID NO: 1), an HCDR2 region comprising the sequence NPYNDG (SEQ ID NO: 2), an HCDR3 region comprising the sequence GTYYYGTRVFDY (SEQ ID NO: 3), an LCDR1 region comprising the sequence RSSKSLQNVNGNTYLY (SEQ ID NO: 4), an LCDR2 region comprising the sequence RMSNLNS (SEQ ID NO: 5), and an LCDR3 region comprising the sequence MQHLEYPIT (SEQ ID NO: 6).
14 : The method of claim 1 wherein said anti-CD19 antibody comprises a variable heavy chain of the sequence
(SEQ ID NO: 7)
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGY
INPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGT
YYYGTRVFDYWGQGTLVTVSS
and a variable light chain of the sequence
(SEQ ID NO: 8)
DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQ
LLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYP
ITFGAGTKLEIK.
15 : The method of claim 1 wherein said anti-CD19 antibody comprises a heavy chain having the sequence
(SEQ ID NO: 11)
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGY
INPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGT
YYYGTRVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
MLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
K
and a light chain having the sequence
(SEQ ID NO: 12)
DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQ
LLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYP
ITFGAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK
VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE
VTHQGLSSPVTKSFNRGEC.
16 : The method of claim 1 wherein said anti-CD19 antibody is administered at least bi-weekly at an amount of 12 mg/kg per dose and wherein lenalidomide is administered daily at an amount of 25 mg.
17 : The method of claim 13 wherein said anti-CD19 antibody comprises a variable heavy chain of the sequence
(SEQ ID NO: 7)
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGY
INPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGT
YYYGTRVFDYWGQGTLVTVSS
and a variable light chain of the sequence
(SEQ ID NO: 8)
DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQ
LLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYP
ITFGAGTKLEIK.
18 : The method of claim 17 wherein said anti-CD19 antibody comprises a heavy chain having the sequence
(SEQ ID NO: 11)
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGY
INPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGT
YYYGTRVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQF
NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREP
QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP
MLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
K
and a light chain having the sequence
(SEQ ID NO: 12)
DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQ
LLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYP
ITFGAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK
VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE
VTHQGLSSPVTKSFNRGEC.