COMBINATIONS OF CD33 ANTIBODY DRUG CONJUGATES WITH HYPOMETHYLATING AGENTS

1 . A method of treating CD33 expressing acute myeloid leukemia (AML) in a subject in need of such treatment, the method comprising the step of administering a hypomethylating agent and 10 μg/kg of a CD33 antibody drug conjugate (ADC), wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent, and wherein the hypomethylating agent is selected from the group consisting of 5-azacytidine and 5-aza-2-deoxycytidine.

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

3 . The method of claim 1 , wherein the hypomethylating agent is 5-azacytidine.

4 . The method of claim 3 , wherein the 5-azacytidine is administered at a concentration between 50-100 mg/m 2 .

5 . The method of claim 3 , wherein the 5-azacytidine is administered at a concentration of about 75 mg/m 2 .

6 . The method of claim 4 , wherein the 5-azacytidine is administered at a concentration of 75 mg/m 2 .

7 . The method of claim 1 , wherein the hypomethylating agent is 5-aza-2-deoxycytidine.

8 . The method of claim 7 , wherein the 5-aza-2-deoxycytidine is administered at a concentration between 15-25 mg/m 2 .

9 . The method of claim 7 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of about 20 mg/m 2 .

10 . The method of claim 7 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of 20 mg/m 2 .

11 . The method of claim 1 , wherein the subject is 75 years or older.

12 . A method of treating CD33-expressing secondary acute myeloid leukemia (AML) in a subject in need of such treatment, the method comprising the step of administering a hypomethylating agent and between 20-40 μg/kg of a CD33 antibody drug conjugate (ADC), wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent, and wherein the hypomethylating agent is 5-aza-2-deoxycytidine.

13 . The method of claim 12 , wherein the PBD cytotoxic agent has the formula

14 . The method of claim 12 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of about 20 mg/m 2 .

15 . The method of claim 12 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of 20 mg/m 2 .

16 . The method of claim 12 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of about 20 mg/m 2 .

17 . The method of claim 12 , wherein the CD33-ADC is administered at 20 μg/kg.

18 . The method of claim 12 , wherein the CD33-ADC is administered at 30 μg/kg.

19 . The method of claim 12 , wherein the CD33-ADC is administered at 40 μg/kg.

20 . The method of claim 12 , wherein the subject is younger than 75 years old.

21 . A method of treating CD33-expressing relapsed or refractory acute myeloid leukemia (AML) in a subject in need of such treatment, the method comprising the step of administering a hypomethylating agent and between 20-40 μg/kg of a CD33 antibody drug conjugate (ADC), wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent, and wherein the hypomethylating agent is 5-aza-2-deoxycytidine.

22 . The method of claim 21 , wherein the PBD cytotoxic agent has the formula

23 . The method of claim 21 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of about 20 mg/m 2 .

24 . The method of claim 21 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of 20 mg/m 2 .

25 . The method of claim 21 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of about 20 mg/m 2 .

26 . The method of claim 21 , wherein the CD33-ADC is administered at 20 μg/kg.

27 . The method of claim 21 , wherein the CD33-ADC is administered at 30 μg/kg.

28 . The method of claim 21 , wherein the CD33-ADC is administered at 40 μg/kg.

29 . The method of claim 21 , wherein the subject is younger than 75 years old.