**8.2 Bortezomib**

Bortezomib (Velcade) is the first proteasome inhibitor approved by FDA in May 2003. A trial phase I explored bortezomib for its tolerance and safety in multiple myeloma, lymphoma, leukemia and lung cancers [64]. Bortezomib showed safely tolerability with few side effects such as general weakness, fever, fatigue, decreased sensation and paresthesia, nausea, vomiting and thrombocytopenia. Amazing response rate (35%) and response duration reaching to more than 1 year in intensely pretreated multiple myeloma patients were reported in the SUMMIT phase II trial [65].

## **8.3 Carfilzomib**

Carfilzomib is a new intravenous agent approved by FDA in 2018 for multiple myeloma of proteasome inhibitors like bortezomib. It should be given with dexamethasone or with dexamethasone and lenalidomide in refractory or relapsed multiple myeloma. In differentiate carfilzomib with bortezomib, appears a better selectivity to the proteasome, covering more of the proteolytic subunits. The common side effects are mild to moderate fever, cytopenia, diarrhea, headache and swelling in hands and feet [66].

## **8.4 Ixazomib**

FDA approved ixazomib in 2015 as the first an oral proteasome inhibitor. Ixazomib used in the same time with dexamethasone and lenalidomide for the treatment patients with refractory or relapsed multiple myeloma [67].

#### **8.5 Immunomodulatory drugs (IMiDs)**

The presentation of immunomodulatory drugs (IMiDs), assist progressed long-term survival of patients with multiple myeloma. Thalidomide and its derivatives, lenalidomide and pomalidomide possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, anti-inflammatory and antiproliferative effects.

#### **8.6 Monoclonal antibodies (MoAbs)**

Presentation of the primary mAb different therapy of multiple myeloma started a modern time in multiple myeloma therapy. Daratumumab, focusing on CD38 as an exceedingly and constantly expressed surface antigen of myeloma, is the primary counter acting agent that was approved by the FDA for the treatment of newly-diagnosed multiple myeloma and also for refractory and relapsed myeloma patients [68]. Elotuzumab, targeting signaling lymphocytic activation molecule F7 (SLAMF7), has been endorsed in combination with lenalidomide and dexamethasone for therapy of myeloma patients in relapse or refractory to treatment [69].

#### **8.7 Histone-deacetylase (HDAC) inhibitors**

An assortment of epigenetic changes together with hereditary changes is basic for malignant growth and proliferation. Altering acetylation status of histones is, close by DNA methylation, an option to gene alteration and blocks gene transcription and inhibits differentiation, providing a rationale for developing HDAC inhibitors. Panobinostat was excessively attempted with different mixes in a few clinical stage I/II trials.

**131**

**Author details**

Safa Shukry1

provided the original work is properly cited.

\*, Fadhel Hariri<sup>2</sup>

3 National Oncology Center, Sana'a, Yemen

\*Address all correspondence to: safa\_shukry@yahoo.com

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

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Abdul Wahab Al-Nehmi3

1 Faculty of Medicine and Health Sciences, University of Aden, Aden, Yemen

2 Supreme Authority of Medicines, Ministry of Public Health, Aden, Yemen

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

*Advances in Hematologic Malignancies*

Bortezomib (Velcade) is the first proteasome inhibitor approved by FDA in May 2003. A trial phase I explored bortezomib for its tolerance and safety in multiple myeloma, lymphoma, leukemia and lung cancers [64]. Bortezomib showed safely tolerability with few side effects such as general weakness, fever, fatigue, decreased sensation and paresthesia, nausea, vomiting and thrombocytopenia. Amazing response rate (35%) and response duration reaching to more than 1 year in intensely pretreated

Carfilzomib is a new intravenous agent approved by FDA in 2018 for multiple myeloma of proteasome inhibitors like bortezomib. It should be given with dexamethasone or with dexamethasone and lenalidomide in refractory or relapsed multiple myeloma. In differentiate carfilzomib with bortezomib, appears a better selectivity to the proteasome, covering more of the proteolytic subunits. The common side effects are mild to moderate fever, cytopenia, diarrhea, headache and

FDA approved ixazomib in 2015 as the first an oral proteasome inhibitor. Ixazomib used in the same time with dexamethasone and lenalidomide for the

The presentation of immunomodulatory drugs (IMiDs), assist progressed long-term survival of patients with multiple myeloma. Thalidomide and its derivatives, lenalidomide and pomalidomide possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, anti-inflammatory and anti-

Presentation of the primary mAb different therapy of multiple myeloma started

An assortment of epigenetic changes together with hereditary changes is basic for malignant growth and proliferation. Altering acetylation status of histones is, close by DNA methylation, an option to gene alteration and blocks gene transcription and inhibits differentiation, providing a rationale for developing HDAC inhibitors. Panobinostat was excessively attempted with different mixes in a few clinical

a modern time in multiple myeloma therapy. Daratumumab, focusing on CD38 as an exceedingly and constantly expressed surface antigen of myeloma, is the primary counter acting agent that was approved by the FDA for the treatment of newly-diagnosed multiple myeloma and also for refractory and relapsed myeloma patients [68]. Elotuzumab, targeting signaling lymphocytic activation molecule F7 (SLAMF7), has been endorsed in combination with lenalidomide and dexamethasone for therapy of myeloma patients in relapse or refractory to treatment [69].

treatment patients with refractory or relapsed multiple myeloma [67].

multiple myeloma patients were reported in the SUMMIT phase II trial [65].

**8.2 Bortezomib**

**8.3 Carfilzomib**

**8.4 Ixazomib**

proliferative effects.

swelling in hands and feet [66].

**8.5 Immunomodulatory drugs (IMiDs)**

**8.6 Monoclonal antibodies (MoAbs)**

**8.7 Histone-deacetylase (HDAC) inhibitors**

**130**

stage I/II trials.
