**6. Some target therapy experience in lymphoproliferative neoplasms**

### **6.1 Rituximab in the treatment of non-Hodgkin's lymphoma**

**Rituximab** (RTX), a chimeric mouse anti-human monoclonal antibodies (MoAbs) targets the CD20 antigen expressed on the neoplastic B cells of leukemia and lymphoma. Rituximab approved by FDA n 1997 for the treatment of B-cell CD20 positive relapsed and refractory of indolent follicular lymphoma, and the European Medicines Agency approved rituximab in June 1998 for chemoresistant or relapsed NHL and for therapy of patients with stage III/IV [7].

The expression of CD20 is varies according to type of cancer (expression in follicular lymphoma is very high, while in chronic lymphocytic leukemia is low). The R-CHOP combination chemotherapy protocol (rituximab, cyclophosphamide, oncovin adriamycin and prednisone) has shown better survival than CHOP alone for treatment of high grade diffuse large cell lymphoma (DLBCL).

#### **6.2 Alemtuzumab for** *patients* **chronic lymphocytic leukemia**

**Alemtuzumab** is a recombinant humanized immunoglobulin MoAb that targets the cell-surface CD52 antigen, has indicated promising outcomes. CD52 is expressed at high levels on normal healthy cells and on CLL cells. Alemtuzumab initially received FDA-approved in September 2007 for treatment of B-CLL patients who are refractory to chemotherapy (fludarabine-*refractory* CLL) [30].

#### **6.3 Milatuzumab in the treatment of multiple myeloma**

**Milatuzumab** is an anti-CD74 monoclonal antibody express the CD47 antigen. Anti-CD47 antibodies have emerged in recent years as a new class of checkpoint inhibitors that may be useful target therapy of hematological malignancies and more effective in treatment of MM, CLL and NHL [31]. Milatuzumab in single monotherapy or in combination with bortezomib is very effective in multiple myeloma.

#### **6.4 Epratuzumab**

Epratuzumab targets the CD22 antigen on B lymphocytes and has additionally been utilized against refractory or relapsed DLBCL patients to rituximab and can be given as monotherapy or in combination with rituximab or standard chemotherapy achieved complete remission in 60% of patients [32].

**5**

*Introductory Chapter: Advances in Hematologic Malignancies*

**6.5 Inotuzumab ozogamicin for Philadelphia+ ALL**

Like gemtuzumab ozogamicin, inotuzumab ozogamicin (Besponsa), an antibody/chemotherapy conjugate that internalizes into the tumor cells upon binding to CD22 on the cell surface. "It's carrying a CD22 Trojan horse to the cell, discharging the payload there (the microtubule-targeting agent calicheamicin) is a highly potent chemotherapeutic drug belonging to the enediyne class of DNA-damaging cytotoxic agents derived from the soil bacterium *Micromonospora echinospora* ssp. calichensis*.*" Inotuzumab looks encouraging in a number of lymphomas, yet it came to advertise first for relapsed or refractory B-ALL patients. The pivotal multicenter stage III preliminary selected 326 patients with refractory or relapsed ALL CD22+, randomizing them to a standard treatment or inotuzumab ozogamicin [33]. Its recent approval has greatly increased the ability to attain remission long period and represents a significant advance in therapeutic options for treatment of relapsed ALL.

In September, 2017, Copanlisib *was* approved *by the FDA* used to treat of adult patients with recurrent low grade follicular lymphoma who have received at least two previous chemotherapies. Copanlisib is a class I phosphatidylinositol 3-kinase (PI3K) inhibitor with a predominance of PI3K-α and PI3K-δ activity present in

In 2017, ibrutinib (Imbruvica) was approved as the first drug for GVHD after corticosteroid therapies response failure. Ibrutinib is a small-molecule of the B-cell antigen receptor inhibits cell proliferation, and promotes apoptosis of cancer cells through inhibition of Bruton's tyrosine kinase. The daily oral dose of 420 mg with median time response of 12 weeks and overall response rate about 67% [35].

In fact, the new therapeutic progress of chimeric antigen receptor T cell is simultaneously a genetically, mechanically, and cellular therapy. This technique changed the leukocytes of the patient in such a way that they could identify and destroy the cancer cells. Despite a number of side effects, CAR T-Cell therapy will be effective

The purpose of CAR creation is to attack specific target molecules on the surface of cancer cells. They are usually antigens CD19 and CD22, which are designated for malignant cells in leukemia and lymphoma. It is very important that there are no similar molecules on the surface of healthy cells. The patient's own T cells are designed to show antigen receptors as "warheads" to focus on and assault tumor cells tumor cells when infused back into the patient. At the point when T cells perceive their target, they are activated, prompting the release of natural killer cells,

The test of these engineered cells is to avoid inhibitor and suppressive signals from regulatory immune cells, the target cells, and the tumor microenvironment. It is beneficial to make reference to that CAR-T cell can recognize potential antigens in almost all structures including lipid, carbohydrate and protein antigens, which can

for most patients who do not accept any other treatment or in relapses.

cytokines, cytotoxic T lymphocytes, and other effector components.

be joined explicitly by antibodies [36, 37].

*DOI: http://dx.doi.org/10.5772/intechopen.88777*

**6.6 Copanlisib for follicular lymphoma**

**6.7 Ibrutinib in chronic graft-vs.-host disease (GVHD)**

cancerous B cells [34].

**7. CAR T-cell therapy**

*Advances in Hematologic Malignancies*

cytarabine (200 mg/m2

**5.3 Midostaurin in** *FLT3***-mutated AML**

with relapsed or refractory CD33+ AML. Subsequent studies with positive findings resulted in the resurrection of gemtuzumab ozogamicin and its approval in 2017.

Midostaurin was approved on 28 April 2017 by FDA for patients with AML who had FLT3 mutations. Midostaurin is an oral small molecule FLT3 inhibitor that inhibits wild-type and mutant FLT3 kinases as well as a number of other factors. The recommended dose of midostaurin is 50 mg capsules given twice daily on days 8–21, with

for 3 days on (d1–3) and also repeat same dose of midostaurin daily for 2 weeks (day 8–21) in each cycle of consolidation in combination with high dose of cytarabine [29].

**6. Some target therapy experience in lymphoproliferative neoplasms**

**Rituximab** (RTX), a chimeric mouse anti-human monoclonal antibodies (MoAbs) targets the CD20 antigen expressed on the neoplastic B cells of leukemia and lymphoma. Rituximab approved by FDA n 1997 for the treatment of B-cell CD20 positive relapsed and refractory of indolent follicular lymphoma, and the European Medicines Agency approved rituximab in June 1998 for chemoresistant or

The expression of CD20 is varies according to type of cancer (expression in follicular lymphoma is very high, while in chronic lymphocytic leukemia is low). The R-CHOP combination chemotherapy protocol (rituximab, cyclophosphamide, oncovin adriamycin and prednisone) has shown better survival than CHOP alone

**Alemtuzumab** is a recombinant humanized immunoglobulin MoAb that targets the cell-surface CD52 antigen, has indicated promising outcomes. CD52 is expressed at high levels on normal healthy cells and on CLL cells. Alemtuzumab initially received FDA-approved in September 2007 for treatment of B-CLL patients

**Milatuzumab** is an anti-CD74 monoclonal antibody express the CD47 antigen. Anti-CD47 antibodies have emerged in recent years as a new class of checkpoint inhibitors that may be useful target therapy of hematological malignancies and more effective in treatment of MM, CLL and NHL [31]. Milatuzumab in single monotherapy or in combination with bortezomib is very effective in multiple myeloma.

Epratuzumab targets the CD22 antigen on B lymphocytes and has additionally been utilized against refractory or relapsed DLBCL patients to rituximab and can be given as monotherapy or in combination with rituximab or standard chemotherapy

who are refractory to chemotherapy (fludarabine-*refractory* CLL) [30].

**6.1 Rituximab in the treatment of non-Hodgkin's lymphoma**

relapsed NHL and for therapy of patients with stage III/IV [7].

for treatment of high grade diffuse large cell lymphoma (DLBCL).

**6.2 Alemtuzumab for** *patients* **chronic lymphocytic leukemia**

**6.3 Milatuzumab in the treatment of multiple myeloma**

achieved complete remission in 60% of patients [32].

), continuously for 7 days (d1–7) and 60 mg/m2

daunorubicin

**4**

**6.4 Epratuzumab**
