Methods for treating multiple myeloma
The present disclosure provides methods of treating multiple myeloma in an individual, the methods comprising genotyping an HLA allele and a KIR allele in the individual; and, depending on the outcome of the genotyping, administering a multiple myeloma therapy to the individual. In some embodiments, the multiple myeloma therapy comprises an anti-CD38 antibody, lenalidomide, and dexamethasone. The present disclosure provides methods for selecting a multiple myeloma patient for a multiple myeloma therapy. The present disclosure provides methods for identifying a multiple myeloma patient as likely to experience a beneficial clinical outcome from a multiple myeloma therapy.
1. A method of treating an individual having multiple myeloma, the method comprising:
a) determining a genotype of a KIR allele of the individual;
b) determining a genotype of an HLA allele of the individual, and
c) when said determining of steps (a) and (b) indicates that the individual has a 3DL1 KIR allele and an HLA-B Bw4-I80 allele, administering a treatment to the individual, wherein the treatment comprises an anti-CD38 antibody, lenalidomide, and dexamethasone, and
wherein the anti-CD38 antibody comprises VHCDR1 of SEQ ID NO:1 (DYWMQ), VH CDR2 of SEQ ID NO:2 (TIYPGDGDTGYAQKFQG), VH CDR3 of SEQ ID NO:3 (GDYYGSNSLDY), VL CDR1 of SEQ ID NO:4 (KASQDVSTWA), VL CDR2 of SEQ ID NO:5 (SASYRYI), and VL CDR3 of SEQ ID NO:6 (QQHYSPPYT).
2. The method of claim 1 , wherein the anti-CD38 antibody kills a CD38 + cell by apoptosis, by antibody-dependent cell-mediated cytotoxicity (ADCC), or by complement-dependent cytotoxicity (CDC).
3. The method of claim 1 , wherein the anti-CD38 antibody binds CD38 with a kD of 3×10 −9 or greater.
4. The method of claim 1 , wherein the anti-CD38 antibody comprises a humanized heavy chain framework region and/or a humanized light chain framework region.
5. The method of claim 1 , wherein the anti-CD38 antibody comprises a VH region comprising the amino acid sequence set forth in SEQ ID NO:7, and comprises a VL region comprising the amino acid sequence set forth in SEQ ID NO:8.
6. The method of claim 1 , wherein the anti-CD38 antibody comprises a heavy chain region of the isotype IgG1, IgG2, IgG3, or IgG4.
7. The method of claim 1 , further comprising determining the copy number of the HLA-B Bw 4-I80 allele.
8. The method of claim 1 , wherein said administering increases progression-free survival (PFS) and/or increases time to progression (TTP).
9. The method of claim 1 , wherein the multiple myeloma is relapsed refractory multiple myeloma.