Therapeutic Indications

Blood and Bone Marrow Cancers

Blood cancers affect the production and function of blood cells. Most of these cancers start in the bone marrow where blood is produced. Stem cells in the bone marrow mature and develop into three types of blood cells: red blood cells, white blood cells, or platelets. In most blood cancers, the normal blood cell development process is interrupted by uncontrolled growth of an abnormal type of blood cells. These abnormal blood cells, or cancerous cells, prevent blood from performing many of its functions, like fighting off infections or preventing serious bleeding.


The three main types of blood cancers are leukemia, lymphoma and myeloma. Leukemia is a type of cancer of the bone marrow, caused by the proliferation of abnormal cells in the bone marrow. Lymphoma is a type of blood cancer that affects the lymphoid organs where the immune cells are located. Myeloma is a cancer of the bone marrow caused by the proliferation of abnormal plasma cells, which are the cells producing the antibodies.

Acute Lymphoblastic Leukemia (ALL)

ALL is a heterogeneous hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. The proliferation and accumulation of blast cells in the marrow results in suppression of hematopoiesis and, thereafter, anemia, thrombocytopenia, and neutropenia. ALL can start either with early B-cells or T-cells at different stages of maturity. The American Cancer Society’s estimates for ALL in the United States for 2018 (including both children and adults) are about 5,960 new cases of ALL and about 1,470 deaths from ALL. Approximately 85% of ALL cases involve precursor B-cells (B-ALL).

ALL represents 75% to 80% of acute leukemia among children, making it the most common form of childhood leukemia; by contrast, ALL represents approximately 20% of all leukemia among adults. The cure rates and survival outcomes for patients with ALL have improved dramatically over the past several decades, primarily among children. Improvements are largely owed to advances in the understanding of the molecular genetics and pathogenesis of the disease, the incorporation of risk-adapted therapy, and the advent of new, targeted agents. Despite great progress in the development of curative therapies, ALL remains a leading cause of pediatric cancer-related mortality for patients presenting with a relapsed or refractory disease. New therapies are needed to overcome chemotherapy resistance and reduce non-specific treatment associated side effects.

Acute Myeloid Leukemia (AML)

AML is characterized by infiltration of the bone marrow, blood, and other tissues by proliferative, clonal, abnormally and/or poorly differentiated cells of the hematopoietic system called blast cells. These cells interfere with normal hematopoiesis, thus contributing to the bone marrow failure which is the most common underlying cause of death. In the U.S. alone, there were an estimated 21,000 new AML cases in 2017, with 10,000 estimated deaths per year. Although it can occur in children and adults, AML is primarily a disease of the elderly, with an incidence of 15 cases per 100,000 for those over 60 and a median age of patients with AML of 67 years. While complete response rates can be as high as 80% in patients undergoing initial induction cytotoxic chemotherapy, the majority of AML patients will ultimately be diagnosed with relapsed or refractory disease with a poor prognosis. CD123 is highly expressed on acute myeloid leukemia (AML) leukemic stem cells and blast cells, as well as in other hematologic malignancies, and constitutes an attractive target for AML.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

BPDCN is a rare and aggressive hematological neoplasm characterized by the clonal proliferation of precursors of plasmacytoid dendritic cells. The disease may occur at any age, but most patients are elderly men who present with skin lesions and/or involve the lymph nodes, spleen, and bone marrow. The few available data reported indicates that its overall incidence is extremely low, accounting for 0.44% of all hematologic malignancies and 0.7% of cutaneous lymphomas. Moreover, the leukemic form of the disease is a rare phenomenon, representing fewer than 1% of cases of acute leukemia. Given its rarity and only recent recognition as a distinct clinico-pathological entity, no standardized therapeutic approach has been established for BPDCN and the optimal therapy remains to be defined.

Multiple Myeloma (MM)

MM is a clonal plasma cell malignant neoplasm characterized by the proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. This clone of plasma cells proliferates in the bone marrow and often results in extensive skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures. MM accounts for approximately 10% of hematologic malignant disorders. The annual incidence, age-adjusted to the US population, is 4.3 per 100,000, resulting in over 20,000 new patients in the United States each year. The median age at onset is 66 years. Nine drugs have been approved over the past fifteen years for the treatment of MM, substantially expanding the number of treatment regimens available for patients in all stages of the disease. In the last decade, survival of multiple myeloma (MM) patients has markedly improved with a median survival of approximately 5 to 7 years but with major variation depending on a host factors: the stage of the disease, cytogenetic abnormalities, and response to therapy. However, despite this progress, patients with disease refractory to both immunomodulatory drugs (IMiDs) and proteasome inhibitors have a median overall survival (OS) of only 9 months.

Non-Hodgkin lymphoma (NHL)

Non-Hodgkin lymphoma (NHL) is a heterogeneous disease resulting from the malignant transformation of lymphocytes with distinctive morphologic, immunophenotypic, genetic, and clinical features. Non-Hodgkin lymphoma is more common than the other general type of lymphoma — Hodgkin lymphoma. The past several decades have seen a steady increase in incidence rates of NHL, with overall rates in the United States nearly doubling over the period 1975 to 2008. In 2017, there were 72,240 estimated new cases with 20,140 estimated deaths in 2017. In 2014, there were an estimated 661,996 people living with non-Hodgkin lymphoma in the United States. Many different subtypes of non-Hodgkin's lymphoma exist. The most common non-Hodgkin lymphoma subtypes include diffuse large B-cell lymphoma and follicular lymphoma.

B-Non-Hodgkin lymphoma (B-NHL)

Non-Hodgkin lymphoma (NHL) is generally divided into 2 main types, based on whether it starts in B lymphocytes (B cells) or T lymphocytes (T cells). About 90% of people in western countries with lymphoma have B-cell lymphoma. There are many different types of B-cell lymphomas: Diffuse large B-cell lymphoma, Follicular lymphoma, Small lymphocytic lymphoma (and chronic lymphocytic leukemia), Mantle cell lymphoma, Extranodal marginal zone B-cell lymphoma – mucosa-associated lymphoid tissue (MALT) lymphoma, Nodal marginal zone B-cell lymphoma, Splenic marginal zone B-cell lymphoma, Burkitt lymphoma, Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia), Hairy cell leukemia, and Primary central nervous system (CNS) lymphoma.