Claims:
1. A method for the treatment of myalgic encephalomyelitis (ME)/chronic fa tigue syndrome (CFS) comprising administering to a patient in need thereof a therapeutically effective amount of an inhibitory or cytotoxic agent against plasma cells to reduce antibody production.
2. The method according to claim 1 wherein the inhibitory agent or cytotoxic agent against plasma cells to reduce antibody production is not an agent being an antibody directed against CD20, like Rituximab.
3. The method for the treatment of ME/CFS according to claim 1 or 2 where in said inhibitory agent against plasma cells is an inhibitor of the pro- teasome, like the immunoproteasome.
4. The method for the treatment of ME/CFS according to claim 3 wherein the inhibitor of the proteasome is selected from the group of Bortezomib, Car- filzomib, Ixazomib, Oprozomib, Delanzomib, Marizomib.
5. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein the cytotoxic agent against plasma cells is an anti body, like a monoclonal antibody, having cytotoxic activity against plasma cells.
6. The method for the treatment of ME/CFS according to claim 5 wherein said antibodies, like monoclonal antibodies including humanized monoclo nal antibodies, are antibodies directed against CD38 and/or CD319.
7. The method for the treatment of ME/CFS according to claim 6 wherein the CD38 monoclonal antibody is Daratumumab, Isatuximab, MOR202, TAK- 079 or wherein the monoclonal antibody directed against CD319 (SLAMF7) is Elotuzumab.
8. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said agents are adapted for systemic administra tion.
9. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said compounds are adapted for administration to a subject in single therapeutically effective daily doses thereof or multiple of therapeutically effective daily doses.
10. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said compounds are administered in a pharmaceu tically effective dosage systemically.
11. The method according to any one of the preceeding claims wherein the plasma cells are CD20 negative plasma cells not including plasmablasts, in particular, terminally differentiated plasma cells not expressing CD20.
12. The method for the treatment of ME/CFS according to any one of the pre ceding claims where the inhibitory or cytotoxic agents against plasma cells are employed in combination with a B-cell depleting agent, or an inhibitor of B-cell activation.
13. The method for the treatment of ME/CFS according to claim 12 wherein the B-cell depleting agent is a B-cell depleting anti-CD20 antibody or CD20 binding antibody fragment thereof, preferably, a monoclonal anti body or a CD20 binding antibody fragment thereof, like a humanized anti body or antibody fragment thereof, or wherein the B-cell depleting agent is a cytotoxic drug like cyclophosphamide, or wherein the inhibitor of B-cell activation is a Bruton Tyrosine Kinase (BTK) inhibitor, or wherein the in hibitor of B-cell activation is an anti B-cell activating factor (anti-BAFF) an tibody.
14. The method for the treatment of ME/CFS according to any one of claims 12 or 13 wherein the B-cell depleting agent is adapted for administration of one or two infusions twice within two weeks.
15. The method for the treatment of ME/CFS according to any one of claims 12 to 14 wherein the inhibition or cytotoxic agents against plasma cells and the B-cell depleting agent are administered simultaneously, separate ly or sequentially to a subject suffering from chronic fatigue syndrome.
16. The method for the treatment of ME/CFS according to any one of claims 12 to 15 wherein the inhibitory or cytostatic agent against plasma cells is administered subcutaneously, intravenously or orally, and the CD20 B-cell depleting agent or inhibitor of B-cell activation is administered subcutane ously, intravenously or orally.
17. The method for the treatment of ME/CFS according to any one of claims 12 to 16 wherein the B-cell depleting anti-CD20 antibody is selected from Rituximab, Ocrelizumab, Obinutuzumab, Veltuzumab, Ofatumumab, or wherein the inhibitor of B-cell activation is selected from Bruton Tyrosine Kinase (BTK) inhibitors such as Ibrutininb, Evobrutinib, or AVL-292, GDC- 0834, ONO-WG-307, Dasatinib, or wherein the inhibitor of B-cell activation is selected from anti B-cell activating factor (anti-BAFF) antibodies such as Belimumab or Tabalumab, or wherein the inhibitor of B-cell activation is selected from cytotoxic drugs like Cyclophosphamide.
18. The method according to any one of claims 12 to 17 wherein the inhibitory or cytotoxic agent against plasma cells is administered first in a first treatment regimen and, after a period of time without treatment will the in hibitory or cytotoxic agent against plasma cells, the B-cell depleting agent, in particular, an anti-CD20 antibody or CD20 binding antibody fragment is administered for a further period of time.
19. The method according to claim 18 wherein the first therapy regimen with administering the inhibitory or cytotoxic agent against plasma cells com prises at least two courses of treatment with the inhibitory or cytotoxic agent against plasma cells and, thereafter, with a period of time with no treatment regimen, administering at least two courses of anti-CD20 anti body or CD20 binding antibody fragment thereof.
20. An inhibitory or cytotoxic agent against plasma cells as defined in any one of claims 1 to 8 for use in the treatment of chronic fatigue syndrome.
21. A composition containing a combination of i) an inhibitory or cytotoxic agent against plasma cells and ii) a B-cell depleting agent, in particular, a B-cell depleting anti-CD20 antibody, or an inhibitor of B-cell activation such as a Bruton Tyrosine Kinase (BTK) inhibitor, or an inhibitor of B-cell activation such as an anti-BAFF antibody, or an inhibitor of B-cell prolifer ation such as a cytotoxic drug like Cyclophosphamide.
22. The composition according to claim 21 for use in the treatment of ME / CFS.
23. The composition for use according to claim 22 wherein the inhibitory or cytotoxic agent against plasma cells is administered in a first step and the B-cell depleting agent is administered thereafter in a second step.
24. The composition for use according to any one of claims 22 to 23 wherein the inhibitory or cytotoxic agent against plasma cells is an inhibitor of the proteasome, in particular, Bbortezomib, and the B-cell depleting agent is a B-cell depleting anti-CD20 antibody, in particular, Rituximab, Ocrelizumab, Obinutuzumab, Veltuzumab, Ofatumumab.