**7.2 Radioimmunotherapy**

Radioimmunotherapy (RIT) is a safe and effective treatment option that combines the advantages of radiotherapy and immunotherapy and advance the adequacy of anti-CD20 target therapy by combining the antibody with a radioconjugate, yttrium-90 without risk of secondary malignancies.

### *7.2.1 Ibritumomab tiuxetan*

Is a monoclonal antibody of IgG1 kappa with name (Zevalin) and the first radiopharmaceuticals to be approved for patients with NHL of B lymphocytes CD20 molecules. Ibritumomab linking to the metal chelator tiuxetan, a monoclonal antibody (111In Zevalin™, Biogen Idec) stable binding of indium-111 (111In) for radionucleotide tumor possible with 90Y ibritumomab tiuxetan [56].

FDA in February 2002 approved 90Y ibritumomab tiuxetan for treatment of refractory and relapsing indolent follicular lymphoma or transformed lymphoma which include lymphoma refractory to rituximab.

The toxicity of ibritumomab tiuxetan is primarily hematologic, which is both transient and reversible. The common side effects, nausea, vomiting, drug interactions, *diarrhea, cough and dizziness.*

#### *7.2.2 Tositumomab iodine I 131*

Is a CD20 radiotherapeutic targets for treatment of lymphoma patients with positive CD20 especially cases of indolent low grade lymphoma, transformed lymphoma, refractory and relapsed lymphoma and lymphoma refractory to rituximab.

The therapeutic administration protocol contain two separate products of tositumomab and iodine I131 tositumomab which will be given in two different steps include dosimetric dose and therapeutic dose separated by 10 days interval.

A relapsed, refractory, or transformed indolent low grade lymphoma overall response (OR) rates have ranged from approximately 60–80% and CR rates have ranged from about 20–40% and a median duration of response of 2 years [57].

Tositumomab toxicities include severe and prolonged thrombocytopenia and neutropenia as well as increase risk of developing other diseases include hypothyroidism, myelodysplasia, acute leukemia.

In June 2003, Tositumomab approved by FDA for treatment of CD20+ follicular lymphoma, that was relapsed following chemotherapy or lymphomas refractory to rituximab.

#### **7.3 Denileukin diftitox**

Denileukin diftitox (Ontak) is a fusion protein (interleukin 2 and diphtheria toxin) approved by FDA in October 16, 2008, for use as an antineoplastic agent to treat pretreated patients with CD25 positive cutaneous T cell lymphomas that express IL-2 receptors. A phase III clinical trial, had good response and significant improvements in self-rated overall QOL [58].

Denileukin diftitox is available in solution in 2 mL single use vials of 150 μg/mL (300 mcg in 2 mL) under the brand name Ontak. The typical dose of intravenous infusion is 9 or 18 mcg/kg/day given for 8 courses every 3 weeks.

Epratuzumab is an antihuman CD22 IgG1 antibody that targets CD22 antigen, found on the surface of B-lymphocytes antigen, CD22 [59, 60]. This drug, either in single administration or in combination with rituximab, created promising outcomes with complete remission [CR] and an ORR of 67% [49].

#### **7.4 Ofatumumab**

In August 2009, ofatumumab was approved as a high-affinity IgG1 mAb that binds to a membrane-proximal epitope of the CD20 molecule of the B cell with potential anti-neoplastic activity triggering and exhibited greater induction of complementdependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells over expressing CD20 when compared with rituximab [61].

#### **7.5 Obinutuzumab**

Is a unique monoclonal antibody, designed to attach to CD20 antigen expressed on the surface of pre-B- and mature B-lymphocytes of malignant lymphoma and for maintenance treatment of patients previously untreated low grade lymphoma especially follicular type resulted in significant free survival. The post-translational

**129**

**Figure 1.**

*History of multiple myeloma treatment.*

*Target Therapy in Hematological Malignancies DOI: http://dx.doi.org/10.5772/intechopen.84696*

**7.6 Brentuximab vedotin**

**8. Multiple myeloma**

refractory to the treatments.

**8.1 Proteasome inhibitors**

focusing on the tumor infiltration or metastasis.

giogenic impacts, and antitumor immunity activation (**Figure 1**).

activity in patients with CD30<sup>+</sup>

glycoengineering process used in the development of this agent, add to its higher binding affinity for human FcγRIII receptors on immune effector cells and the

An anti-CD30 antibody-drug conjugate and demonstrated significant clinical

Multiple myeloma (MM) is a blood cancer that remains serious disease and it cannot usually be cured because most patients relapse after treatment or become

Novel agents are as of now in advancement for the management of refractory or relapsed multiple myeloma, counting immunomodulatory drugs, monoclonal antibodies, proteasome inhibitors, cell signaling focused on treatments, and procedures

Proteasome inhibitors such as bortezomib target therapy of multiple myeloma the ubiquitin pathway, coming about in cytotoxic damage due to disturbance of protein corruption in myeloma cells. The immunomodulatory agents, thalidomide, lenalidomide, and pomalidomide, are a novel of class of oral target agents impact on myeloma cells through a few components counting coordinate cytotoxicity, antian-

The proteasome is a gigantic highly sophisticated protease complex that degrades

unneeded or damaged proteins by proteolysis. As such, the proteasome plays an important role in critical cellular processes including proliferation, differentiation, cell cycle progression and survival DNA repair, angiogenesis and apoptosis [63]. Three proteasome inhibitors, carfilzomib, bortezomib and ixazomib are approved

by FDA and oprozomib and other agents are in the clinical trials late stages.

classical HL and anaplastic large cell lymphoma (ALCL) (**Tables 4** and **5**).

malignancies, including Reed Sternberg cells in

mAbs to novel targets are being developed with ADCC in mind [62].

glycoengineering process used in the development of this agent, add to its higher binding affinity for human FcγRIII receptors on immune effector cells and the mAbs to novel targets are being developed with ADCC in mind [62].
