ANTI-CD19 THERAPY IN PATIENTS HAVING A LIMITED NUMBER OF NK CELLS

1 . An anti-CD19 antibody for use in the treatment of hematological cancer patients wherein said patients have a peripheral NK cell count at baseline of less or equal to 100 NK cells/μl. use in

2 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to claim 1 , wherein the 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)

3 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to any one of the preceding claims, wherein the 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.

4 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to any one of the preceding claims, wherein the anti-CD19 comprises a heavy chain having the sequence

(SEQ ID NO: 11)

EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGY

INPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGT

YYYGTRVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV

KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPK

PKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTIPP

MLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

and a light chain having the sequence

(SEQ ID NO: 12)

DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQ

LLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYP

ITFGAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK

VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE

VTHQGLSSPVTKSFNRGEC

5 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to any one of the preceding claims, wherein said anti-CD19 antibody is administered in combination with one or more additional pharmaceutical agent.

6 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to claim 5 wherein said pharmaceutical agent is a biologic or a chemotherapeutic agent or a pharmaceutically acceptable salt thereof.

7 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to claim 6 , wherein said one or more pharmaceutical agent is a therapeutic antibody or antibody fragment, a nitrogen mustard, a purine analog, a thalidomide analog, a phosphoinositide 3-kinase inhibitor, a BCL-2 inhibitor, a bruton's tyrosine kinase (BTK) inhibitor or a pharmaceutically acceptable salt thereof.

8 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to claim 7 , wherein said one or more pharmaceutical agent is rituximab, R-CHOP, cyclophosphamide, chlorambucil, uramustine, ifosfamide, melphalan, bendamustine, mercaptopurine, azathioprine, thioguanine, fludarabine, thalidomide, lenalidomide, pomalidomide, idelalisib, duvelisib, copanlisib, ibrutinib, venetoclax or a pharmaceutically acceptable salt thereof.

9 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to any of the preceding claims, wherein said hematologic cancer patient has chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), small lymphocytic lymphoma (SLL) or acute lymphoblastic leukemia (ALL).

10 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to claim 9 , wherein said hematologic cancer patient has non-Hodgkin's lymphoma.

11 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to claim 10 , wherein the non-Hodgkin's lymphoma is selected from the group consisting 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.

12 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to claim 11 , wherein the non-Hodgkin's lymphoma is Relapsed or Refractory Diffuse Large B-cell Lymphoma (r-r DLBCL).

13 . The anti-CD19 antibody for use in the treatment of hematological cancer patients according to any of the preceding claims, wherein said anti-CD19 antibody increases one or more of the following features:

(i) the progression-free survival (PFS),

(ii) the objective response rate (ORR),

(iii) the duration of response (DoR),

(iv) the overall survival (OS),

(v) the time to progression (TTP).

14 . A method of selecting a hematological cancer patient who is predicted to benefit from the therapeutic administration of an anti-CD19 antibody, said method comprising the following steps:

a) providing a blood sample obtained from said patient prior to treatment with said anti-CD19 antibody,

b) determining the peripheral NK cell count, and

c) selecting the patient on the basis of the patient has a peripheral NK cell count at baseline of less or equal to 100 cells/μl.

15 . The method according to claim 14 , further comprising the following step:

d) treatment of the selected patient with an anti-CD19 antibody.