Anti-CD38 antibodies for treatment of light chain amyloidosis and other CD38-positive hematological malignancies
The present invention relates to methods of treatment of light chain amyloidosis and other CD38-positive hematological malignancies with anti-CD38 antibodies.
1. A method of treating a patient having relapsed or refractory light chain amyloidosis (AL), comprising administering to the patient in need thereof an anti-CD38 antibody which is an IgG1 isotype comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5 for a time sufficient to treat relapsed or refractory AL.
2. The method of claim 1 , wherein the patient has been treated with a proteasome inhibitor, cyclophosphamide and/or a corticosteroid.
3. The method of claim 2 , wherein the proteasome inhibitor is bortezomib.
4. The method of claim 2 , wherein the corticosteroid is dexamethasone.
5. The method of claim 1 , wherein the anti-CD38 antibody is administered in combination with a second therapeutic agent.
6. The method of claim 2 , wherein the anti-CD38 antibody is administered in combination with a second therapeutic agent.
7. The method of claim 5 , wherein the second therapeutic agent is a proteasome inhibitor, cyclophosphamide or a corticosteroid.
8. The method of claim 7 , wherein the proteasome inhibitor is bortezomib or ixazomib.
9. The method of claim 7 , wherein the corticosteroid is dexamethasone.
10. The method of claim 5 , wherein the second therapeutic agent is bortezomib, ixazomib, carfilzomib, panobinostat, cyclophosphamide, melphalan, thalidomide, lenalidomide, pomalidomide, dexamethasone or interferon alpha.
11. The method of claim 1 , wherein the anti-CD38 antibody is administered in combination with a proteasome inhibitor, cyclophosphamide and a corticosteroid.
12. The method of claim 11 , wherein the proteasome inhibitor is bortezomib.
13. The method of claim 11 , wherein the proteasome inhibitor is ixazomib.
14. The method of claim 11 , wherein the corticosteroid is dexamethasone.
15. The method of claim 11 , wherein the proteasome inhibitor is bortezomib and the corticosteroid is dexamethasone.
16. The method of claim 11 , wherein the proteasome inhibitor is ixazomib and the corticosteroid is dexamethasone.
17. The method of claim 5 , wherein the anti-CD38 antibody and the second therapeutic agent are administered simultaneously, sequentially or separately.
18. The method of claim 11 , wherein the proteasome inhibitor, cyclophosphamide and the corticosteroid are administered simultaneously, sequentially or separately.
19. The method of claim 1 , wherein the patient is further treated with radiotherapy.
20. The method of claim 1 , wherein the anti-CD38 antibody does not mediate killing of CD34-positive hematopoietic progenitor cells by complement dependent cytotoxicity (CDC).
21. The method of claim 1 , wherein the anti-CD38 antibody induces killing of CD38 positive plasma cells by antibody-dependent cell-mediated cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC), apoptosis, or modulation of CD38 enzymatic activity.
22. The method of claim 1 , wherein the anti-CD38 antibody comprises a heavy chain comprising an amino acid sequence that is 95%, 96%, 97%, 98%, 99%, or 100% identical to that of SEQ ID NO: 12 and a light chain comprising an amino an amino acid sequence that is 95%, 96%, 97%, 98%, 99%, or 100% identical to that of SEQ ID NO: 13.
23. The method of claim 22 , wherein the anti-CD38 antibody comprises the heavy chain of SEQ ID NO: 12 and the light chain of SEQ ID NO: 13.
24. The method of claim 1 , wherein the anti-CD38 antibody is human.
25. The method of claim 1 , wherein the anti-CD38 antibody is administered intravenously.
26. The method of claim 1 , further comprising performing hematopoietic stem cell transplantation (HSCT) after administering the effective amount of anti-CD38 antibody to the patient having relapsed or refractory AL.
27. The method of claim 26 , wherein the HSCT is allogeneic, autologous or syngeneic.
28. The method of claim 26 , wherein the HSCT comprises transplantation of blood stem cells derived from bone marrow, blood or amniotic fluid.
29. The method of claim 26 , wherein the patient has completed chemotherapy and/or radiation therapy prior to HSCT.
30. The method of claim 1 , wherein the anti-CD38 antibody is administered in a pharmaceutical composition comprising the anti-CD38 antibody and a hyaluronidase.
31. A method of induction of selective killing of CD38 + hematological cancer cells and preservation of CD38 + CD34 + hematopoietic stem cells in a patient with relapsed or refractory light chain amyloidosis (AL), comprising:
contacting CD38 + cells of the patient with an anti-CD38 antibody which is an IgG1 isotype comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5;
wherein CD38 + hematological cancer cells within the patient are killed and CD38 + CD34 + hematopoietic stem cells within the patient are preserved.
32. A method of performing a hematopoietic stem cell transplant (HSCT) in a patient with relapsed or refractory light chain amyloidosis (AL), comprising:
introducing hematopoietic stem cells into the patient; and
administering to the patient an anti-CD38 antibody after introduction of the hematopoietic stem cells, the anti-CD38 antibody comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5, wherein the anti-CD38 antibody is an IgG1 isotype and induces killing of CD38 + hematological cancer cells, and wherein CD38 + CD34 + hematopoietic stem cells within the transplant survive.
33. A method of performing a hematopoietic stem cell transplant (HSCT) in a patient with relapsed or refractory light chain amyloidosis (AL), comprising:
administering to the patient an anti-CD38 antibody which is an IgG1 isotype comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5; and
introducing hematopoietic stem cells into the patient after administration of the anti-CD38 antibody, wherein the anti-CD38 antibody induces killing of CD38 + hematological cancer cells, and wherein CD38 + CD34 + hematopoietic stem cells within the transplant survive.