Anti-CD38 antibody and lenalidomide or bortezomib for the treatment of multipe myeloma and NHL
The present disclosure describes a pharmaceutical combination of an anti-CD38 antibody and lenalidomide and a pharmaceutical combination of an anti-CD38 antibody and bortezomib.
1. A synergistic combination of:
(i) an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1) or SYYMN (SEQ ID NO: 14), an HCDR2 region of sequence GISGDPSNTYYADSVKG (SEQ ID NO: 2), an HCDR3 region of sequence DLPLVYTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6) and
(ii) (a) thalidomide, lenalidomide, or pomalidomide, or (b) a proteasome inhibitor,
for use in the treatment of multiple myeloma and/or non-hodgkins lymphoma.
2. A combination according to claim 1 , wherein the antibody comprises a variable heavy chain of the sequence:
(SEQ ID NO: 10)
QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYYMNWVRQAPGKGLEWVSG
ISGDPSNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDL
PLVYTGFAYWGQGTLVTV SS
and a variable light chain of the sequence
(SEQ ID NO: 11)
DIELTQPPSVSVAPGQTARISCSGDNLRHYYVYWYQQKPGQAPVLVIYGD
SKRPSGIPERFSGSNSGNTATLTISGTQAEDEADYYCQTYTGGASLVFGG
GTKLTVLGQ.
3. A combination according to claim 1 , wherein the antibody comprises an IgG1 Fc region.
4. A combination according to claim 1 , wherein the antibody comprises a modified Fc region, wherein said modification enhances ADCC activity.
5. A combination according to claim 1 , wherein said antibody specific for CD38 and said thalidomide, lenalidomide, or pomalidomide, or a proteasome inhibitor, are administered separately.
6. A combination according to claim 1 , which is able to reduce bone lysis with an at least two-fold better efficacy than lenalidomide and/or bortezomib alone.
7. A combination according to claim 1 , wherein the combination comprises thalidomide.
8. A combination according to claim 1 , wherein the combination comprises lenalidomide.
9. A combination according to claim 8 , wherein lenalidomide is administered prior to administration of the antibody specific for CD38.
10. A combination according to claim 9 , wherein lenalidomide is administered at least 72 hours prior to administration of the antibody specific for CD38.
11. A combination according to claim 8 , which is able to mediate killing of CD38-expressing AMO-1 and/or NCI-H929 cells by ADCC in the presence of isolated human PBMCs with an at least two-fold better efficacy than lenalidomide alone.
12. A combination according to claim 1 , comprising said antibody specific for CD38 and a proteasome inhibitor.
13. A combination according to claim 12 , wherein said proteasome inhibitor is bortezomib.
14. A combination according to claim 13 , which is able to mediate killing of CD38-expressing LP-1 and/or NCI-H929 cells by ADCC in the presence of isolated human PBMCs with an at least two-fold better efficacy than bortezomib alone.
15. A synergistic combination of:
an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1), an HCDR2 region of sequence GISGDPSNTYYADSVKG (SEQ ID NO: 2), an HCDR3 region of sequence DLPLVYTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6) and
(ii) lenalidomide,
for use in the treatment of multiple myeloma and/or non-hodgkins lymphoma.
16. A synergistic combination of:
(i) an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1), an HCDR2 region of sequence GISGDPSNTYYADSVKG (SEQ ID NO: 2), an HCDR3 region of sequence DLPLVYTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6) and
(ii) pomalidomide,
for use in the treatment of multiple myeloma and/or non-hodgkins lymphoma.
17. A combination according to claim 1 , wherein the combination comprises pomalidomide.
18. A combination according to claim 12 , wherein said proteasome inhibitor is carfilzomib.
19. A synergistic combination of:
(i) an antibody specific for CD38 comprising an HCDR1 region of sequence GFTFSSYYMN (SEQ ID NO: 1), an HCDR2 region of sequence GISGDPSNTYYADSVKG (SEQ ID NO: 2), an HCDR3 region of sequence DLPLVYTGFAY (SEQ ID NO: 3), an LCDR1 region of sequence SGDNLRHYYVY (SEQ ID NO: 4), an LCDR2 region of sequence GDSKRPS (SEQ ID NO: 5), and an LCDR3 region of sequence QTYTGGASL (SEQ ID NO: 6) and
a thalidomide analog,
for use in the treatment of multiple myeloma and/or non-hodgkins lymphoma.