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 light chain amyloidosis (AL) in a newly diagnosed AL patient, comprising administering to the patient a pharmaceutical composition comprising an anti-CD38 antibody and a hyaluronidase for a time sufficient to treat the AL, wherein:
a) the anti-CD38 antibody is of 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;
b) the hyaluronidase is rHuPH20 recombinant hyaluronidase; and
c) the pharmaceutical composition is administered in combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD).
2. The method of claim 1 , wherein the anti-CD38 antibody and CyBorD are administered simultaneously.
3. The method of claim 1 , wherein the anti-CD38 antibody and CyBorD are administered sequentially or separately.
4. The method of claim 1 , wherein the cyclophosphamide, the bortezomib and the dexamethasone are administered simultaneously.
5. The method of claim 1 , wherein the cyclophosphamide, the bortezomib and the dexamethasone are administered sequentially or separately.
6. The method of claim 1 , wherein the patient is undergoing hematopoietic stem cell transplantation (HSCT).
7. The method of claim 6 , wherein the HSCT is allogeneic.
8. The method of claim 6 , wherein the HSCT is autologous or syngeneic.
9. The method of claim 6 , wherein the HSCT comprises transplantation of blood stem cells derived from bone marrow, blood or amniotic fluid.
10. The method of claim 6 , wherein the anti-CD38 antibody is administered prior to HSCT.
11. The method of claim 6 , wherein the anti-CD38 antibody is administered during or after HSCT.
12. The method of claim 6 , wherein the patient has completed chemotherapy and/or radiation therapy prior to HSCT.
13. The method of claim 1 , wherein the patient is further treated with radiotherapy.
14. 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).
15. 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.
16. The method of claim 1 , wherein the anti-CD38 antibody binds at least to the region SKRNIQFSCKNIYR (SEQ ID NO: 2) and the region EKVQTLEAWVIHGG (SEQ ID NO: 3) of human CD38 SEQ ID NO: 1.
17. 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 acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to that of SEQ ID NO: 13.
18. The method of claim 1 , wherein the anti-CD38 antibody comprises the heavy chain of SEQ ID NO: 12 and the light chain of SEQ ID NO: 13.