Dosage regimen for administering a CD19XCD3 bispecific antibody

1. A method for treating malignant CD19 positive lymphocytes in a human patient identified as having a peripheral blood B:T cell ratio of about 1:5 or lower before treatment to identify patients at risk of developing adverse effects, wherein said B:T cell ratio can be determined by the following steps:

i) Determining the total B cell number in a peripheral blood sample of said human patient;

ii) Determining the total T cell number in a peripheral blood sample of said human patient;

iii) Calculating the ratio of the total B cell number of step i) and the total T cell number of step ii) in order to obtain a B:T cell ratio,

said method comprising:

(a) administering a first dose of a CD19×CD3 bispecific antibody for a first period of time to said human patient; and consecutively

(b) administering a second dose of said antibody for a second period of time to said human patient;

wherein said second dose exceeds said first dose, and wherein said CD19×CD3 bispecific antibody is MT103 (Blinatumomab).

2. The method of claim 1 , wherein said method ameliorates and/or prevents an adverse effect mediated by the administration of a CD19×CD3 bispecific antibody to said human patient having a B:T cell ratio of about 1:5 or lower.

3. The method of claim 1 , wherein said CD19 positive lymphocytes comprise malignant CD19 positive lymphoma or leukemia cells.

4. The method of claim 1 , wherein the route of administration in step (a) and/or the route of administration in step (b) is intravenous.

5. The method of claim 2 , wherein said adverse effect is characterized by a neurological reaction.

6. The method of claim 5 , wherein said neurological reaction is one or more selected from the group consisting of: confusion, ataxia, disorientation, dysphasia, aphasia, speech impairment, cerebellar symptoms, tremor, apraxia, seizure, grand mal convulsion, palsy, and balance disorder.

7. The method of claim 1 , wherein said second period of time exceeds said first period of time.

8. The method of claim 1 , wherein said first period of time exceeds 3 days.

9. The method of claim 1 , wherein said first period of time is between 3 days and 10 days.

10. The method of claim 1 , wherein said second period of time exceeds 18 days.

11. The method of claim 1 , wherein said second period of time is between 18 days and 81 days.

12. The method of claim 1 , wherein said first period of time is between 3 days and 10 days, and said second period of time is between 18 days and 81 days.

13. The method of claim 12 , wherein said first period of time is 7 days and said second period of time is 21 or 49 days.

14. The method of claim 1 , wherein said first dose is between 1 and 15 μg/m 2 /d.

15. The method of claim 1 , wherein said second dose is between 15 and 60 μg/m 2 .

16. The method of claim 1 , further comprising administering after a first and second dose for a first and second period of time a third dose of said antibody for a third period of time.

17. The method of claim 16 , wherein said first period of time exceeds 3 days.

18. The method of claim 16 , wherein said first period of time is between 3 days and 10 days.

19. The method of claim 16 , wherein said second period of time exceeds 3 days.

20. The method of claim 16 , wherein said second period of time is between 3 days and 10 days.

21. The method of claim 16 , wherein said third period of time exceeds 8 days.

22. The method of claim 16 , wherein said third period of time is between 8 days and 78 days.

23. The method of claim 16 , wherein said first period of time is between 3 days and 10 days, and said second period of time is between 3 days and 10 days, and said third period of time is between 8 days and 78 days.

24. The method of claim 23 , wherein said first period of time is 7 days, said second period of time is 7 days and said third period of time is 14 or 42 days.

25. The method of claim 16 , wherein said first dose is between 1 and 15 μg/m 2 /d.

26. The method of claim 16 , wherein said second dose is between 1 and 15 μg/m2/d.

27. The method of claim 16 , wherein said third dose is between 15 and 60 μg/m 2 /d.

28. The method of claim 16 , wherein the route of administration of the third dose is intravenous.

29. The method of claim 3 , wherein the lymphoma is indolent or aggressive B cell non-Hodgkin lymphoma (B NHL), mantle cell lymphoma (MCL) or chronic lymphatic leukemia (CLL).

30. The method of claim 3 , wherein the leukemia is B-lineage acute lymphoblastic leukemia (ALL).

31. The method of claim 16 , wherein said antibody is administered at a first dose of 5 μg/m 2 /d, followed by a second dose of 15 μg/m 2 /d and consecutively followed by a third dose of 60 μg/m 2 /d.

32. A method for ameliorating or preventing an adverse effect mediated by the administration of a CD19×CD3 bispecific antibody to a human patient having a B:T cell ratio of about 1:5 or lower, said method comprising:

(a) determining the ratio of total B cells to total T cells in a peripheral blood sample from said human patient to identify patients at risk of developing an adverse effect;

(b) identifying said human patient as having an increased risk of potential adverse effects when the ratio of B:T cells is about 1:5 or less before treatment;

(c) administering a first dose of said antibody for a first period of time to said patient identified in (b),

and consecutively;

(d) administering a second dose of said antibody for a second period of time;

wherein said second dose exceeds said first dose, and wherein said CD19×CD3 bispecific antibody is MT103 (Blinatumomab).

33. The method of claim 32 , wherein said adverse effect is characterized by a neurological reaction.

34. The method of claim 33 , wherein said neurological reaction is one or more selected from the group consisting of: confusion, ataxia, disorientation, dysphasia, aphasia, speech impairment, cerebellar symptoms, tremor, apraxia, seizure, grand mal convulsion, palsy, and balance disorder.