Combination of CD33 antibody drug conjugates with chemotherapeutic agents

1. A method of treating CD33 expressing acute myeloid leukemia (AML) in a subject in need of such treatment, the method comprising:

1) administering an anthracycline antibiotic, and a CD33 antibody drug conjugate (ADC) in an induction period of seven days, wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent, and wherein 10 μg/kg or 20 μg/kg of the CD33-ADC is administered on day one of the induction period and 10 μg/kg of the CD33-ADC is administered on day four of the induction period;

wherein the anthracycline antibiotic: 1) is cytarabine and is administered on induction days 1-7; or 2) is daunorubicin and is administered on induction days 1-3; and

2) after the induction period, administering the CD33-ADC and cytarabine in up to four consolidation cycles each comprising seven days, wherein the CD33-ADC is administered on day 1 of each consolidations cycle at 10 μg/kg or 20 μg/kg, and wherein cytarabine is administered on days 1, 3, and 5 of each consolidation cycles at 3 mg/m 2 /day.

2. The method of claim 1 , wherein the PBD cytotoxic agent has the formula

3. The method of claim 1 , wherein the anthracycline antibiotic is daunorubicin and is administered at 60 mg/m 2 /day on induction days 1-3.

4. The method of claim 1 , wherein the anthracycline antibiotic is cytarabine and is administered at 100 mg/m 2 /day on induction days 1-7.

5. The method of claim 1 , wherein the humanized 2H12 antibody comprises a light chain variable region of SEQ ID NO:1 and a heavy chain variable region of SEQ ID NO:2.

6. A method of treating CD33 expressing acute myeloid leukemia (AML) in a subject in need of such treatment, the method comprising:

1) administering an anthracycline antibiotic, and a CD33 antibody drug conjugate (ADC) in an induction period of seven days, wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent, and wherein 30 μg/kg or 40 μg/kg of the CD33-ADC is administered on day one of the induction period;

wherein the anthracycline antibiotic: 1) is cytarabine and is administered on induction days 1-7; or 2) is daunorubicin and is administered on induction days 1-3; and

2) after the induction period, administering the CD33-ADC and cytarabine in up to four consolidation cycles each comprising seven days, wherein the CD33-ADC is administered on day 1 of each consolidations cycle at 10 μg/kg or 20 μg/kg, and wherein cytarabine is administered on days 1, 3, and 5 of each consolidation cycles at 3 mg/m 2 /day.

7. The method of claim 6 , wherein the PBD cytotoxic agent has the formula

8. The method of claim 6 , wherein the anthracycline antibiotic is daunorubicin and is administered at 60 mg/m 2 /day on induction days 1-3.

9. The method of claim 6 , wherein the anthracycline antibiotic is cytarabine and is administered at 100 mg/m 2 /day on induction days 1-7.

10. The method of claim 6 , wherein the humanized 2H12 antibody comprises a light chain variable region of SEQ ID NO:1 and a heavy chain variable region of SEQ ID NO:2.

11. The method of claim 1 , wherein the method further comprising, after the consolidation cycles, administering the CD33-ADC in up to eight maintenance cycles each comprising forty two days, wherein the CD33-ADC is administered at 5 μg/kg on day 1 of each maintenance cycle.

12. The method of claim 6 , wherein the method further comprising, after the consolidation cycles, administering the CD33-ADC in up to eight maintenance cycles each comprising forty two days, wherein the CD33-ADC is administered at 5 μg/kg on day 1 of each maintenance cycle.