Abstract: The present invention relates to a method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19xCD3 bispecific single chain antibody construct to an adult patient in the need thereof.

Abstract: The present invention relates to a method for the treatment, amelioration or elimination of pediatric acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19×CD3 bispecific single chain antibody construct to a pediatric ALL patient in the need thereof.

Abstract: The present invention relates to a glucocorticoid (GC) for use in the amelioration, treatment or prophylaxis of neurological/psychiatric adverse events caused by a CD3 binding domain. Kits comprising a GC, a CD3 binding domain and instructions for use which indicate that the GC is to be employed for the treatment amelioration and/or prophylaxis of neurological adverse events caused by said CD3 binding domain, are also disclosed.

Abstract: The present invention relates to a method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19×CD3 bispecific single chain antibody construct to an adult patient in the need thereof.

Abstract: The present invention relates to a method of treating Burkitt lymphoma or leukemia in a patient, the method comprising administering to said patient a composition comprising a CD19×CD3 bispecific antibody in at least one treatment cycle, wherein the treatment cycle comprises administering a first dose of 15 ?g/m2/d of the CD19×CD3 bispecific antibody for a first period of time of 4 days, and administering after the first dose a second dose of 60 Kg/m2/d of the CD19×CD3 bispecific antibody for a second period of time, wherein the second period of time exceeds the first period of time.

Abstract: The present disclosure relates to an antibody construct comprising a first domain which binds to BCMA and a second domain which binds to CD3, for use in the treatment or amelioration of a BCMA positive neoplasm, wherein the antibody construct is administered at a specified dose in at least one cycle, wherein one cycle comprises a specified period of administration of the antibody construct. Moreover, the disclosure relates to a method for the treatment of a BCMA positive neoplasm comprising administering a specified amount of such antibody construct, and the use of such antibody construct for the manufacture of a medicament for the treatment of a BCMA positive neoplasm.

Abstract: The present invention relates in essence to a compound which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells in a patient. Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated.

Abstract: The present invention relates to a method for risk-stratifying subjects suffering from B-precursor acute lymphoblastic leukemia (ALL), wherein said subjects are intended for a therapy comprising administration of a CD3 binding domain. Risk-stratification is based on the determination of the amount blast cells in a bone marrow sample from said subject, and/or on the determination of the number of blast cells per 1 ?l in a CSF sample from said subject. According to the category into which subjects are risk-stratified, said subjects can be appropriately treated, while their risk of a potential adverse neurological reaction can be reduced or even excluded.

Abstract: The present invention provides a bispecific construct comprising a first binding domain specifically binding to CD33 and a second binding domain specifically binding to CD3 for use in a method for the treatment of myeloid leukemia, wherein the construct is administered for a maximal period of 14 days followed by a period of at least 14 days without administration of the construct. Moreover, the invention provides a method for the treatment of myeloid leukemia comprising the administration of a therapeutically efficient amount of such bispecific construct and the use of such bispecific construct for the preparation of a pharmaceutical composition for the treatment of myeloid leukemia.

Abstract: The present invention provides means and methods for treating diffuse large B cell lymphoma (DLBCL). Specifically, a bispecific CD19×CD3 antibody which engages T cells via its CD3 binding portion and concomitantly binds to CD19 on the surface of, in particular, lymphoma cells via its CD19 binding portion (i.e. a bispecific T cell engager, “BiTE”) is administered for use in the treatment of tumorous mass of lymophoreticular tissue and/or extranodal lymphoma caused by DLBCL in a patient.

Abstract: The disclosure provides a method for assessing the risk of potential adverse effects for a human patient mediated by the administration of a CD19×CD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient. The disclosure also provides a method for administering a CD19×CD3 bispecific antibody to a human patient having a B:T cell ratio of about 1:5 or lower, comprising administering doses in a dosing regimen. This dosing regimen can be applied in methods for treating malignant CD19 positive lymphocytes or for ameliorating and/or preventing an adverse effect mediated by the administration of said bispecific antibody. The Also provided is a pharmaceutical package or kit comprising a first dose and a second dose and optionally a third dose of said antibody.

Abstract: The present invention relates to a method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19×CD3 bispecific single chain antibody construct to an adult patient in the need thereof.

Abstract: The present invention relates to a glucocorticoid (GC) for use in the amelioration, treatment or prophylaxis of neurological/psychiatric adverse events caused by a CD3 binding domain. Kits comprising a GC, a CD3 binding domain and instructions for use which indicate that the GC is to be employed for the treatment amelioration and/or prophylaxis of neurological adverse events caused by said CD3 binding domain, are also disclosed.

Abstract: The present invention provides a bispecific construct comprising a first binding domain specifically binding to CD33 and a second binding domain specifically binding to CD3 for use in a method for the treatment of myeloid leukemia, wherein the construct is administered for a maximal period of 14 days followed by a period of at least 14 days without administration of the construct. Moreover, the invention provides a method for the treatment of myeloid leukemia comprising the administration of a therapeutically efficient amount of such bispecific construct and the use of such bispecific construct for the preparation of a pharmaceutical composition for the treatment of myeloid leukemia.

Abstract: The present invention relates to a glucocorticoid (GC) for use in the amelioration, treatment or prophylaxis of neurological/psychiatric adverse events caused by a CD3 binding domain. Kits comprising a GC, a CD3 binding domain and instructions for use which indicate that the GC is to be employed for the treatment amelioration and/or prophylaxis of neurological adverse events caused by said CD3 binding domain, are also disclosed.

Abstract: The present invention relates in essence to a compound which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells in a patient. Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated.

Abstract: The present invention relates in essence to use of a compound, which decreases or inhibits the binding of mammalian T-cells to mammalian endothelial cells for use in a method of prophylaxis and/or amelioration and/or treatment of clinical adverse events caused by a therapy which comprises re-directing of T-cells against target cells in a patient. Such a therapy includes, but is not limited to, treatment with an antibody comprising a CD3 binding domain, such as a CD20×CD3 or a CD19×CD3 bispecific single chain antibody, e.g., blinatumomab (MT-103). Methods of treatment of patients having or being at risk of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells are also contemplated, as are methods of identifying a compound for administration in the methods of prophylaxis, amelioration and/or treatment.

Abstract: The present invention relates to a method for risk-stratifying subjects suffering from B-precursor acute lymphoblastic leukemia (ALL), wherein said subjects are intended for a therapy comprising administration of a CD3 binding domain. Risk-stratification is based on the determination of the amount blast cells in a bone marrow sample from said subject, and/or on the determination of the number of blast cells per 1 ?l in a CSF sample from said subject. According to the category into which subjects are risk-stratified, said subjects can be appropriately treated, while their risk of a potential adverse neurological reaction can be reduced or even excluded.

Abstract: The present invention relates to a pentosanpolysulfate (PPS) or a pharmaceutically acceptable salt thereof for use in the amelioration, treatment, or prevention of adverse neurological events caused by administering an antibody or fragment thereof comprising a CD3 binding domain, including a CD19 x CD3 bispecific single chain antibody, such as blinatumomab. PPS is a semi-synthetically produced heparin-like macromolecular carbohydrate derivative, which chemically and structurally resembles glycosaminoglycans. Kits comprising a PPS, an antibody or fragment thereof comprising a CD3 binding domain, and instructions for administration, which indicate that the PPS is to be employed for the amelioration, treatment or prevention of adverse neurological events caused by administering the antibody or fragment thereof comprising said CD3 binding domain, are also disclosed.

Abstract: The present invention provides means and methods for treating diffuse large B cell lymphoma (DLBCL). Specifically, a bispecific CD19×CD3 antibody which engages T cells via its CD3 binding portion and concomitantly binds to CD19 on the surface of, in particular, lymphoma cells via its CD19 binding portion (i.e. a bispecific T cell engager, “BiTE”) is administered for use in the treatment of tumorous mass of lymophoreticular tissue and/or extranodal lymphoma caused by DLBCL in a patient.