Hematologic Oncology

Dr. Bennett and colleagues have provided a thorough and balanced history of the rise and fall of erythropoietin-stimulating agents (ESAs) in cancer-associated anemia. Their review encourages us to think about the lessons learned from this history-lessons about medical progress, the importance of clinical research in guiding clinical practice, and the role of the US Food and Drug Administration (FDA) in protecting patients

The perception and reality of the clinical value of erythropoiesis-stimulating agents (ESAs) in cancer supportive care have undergone a dramatic transformation since their initial use in 1990. The perception of ESA value in patients has evolved from panacea to miscreant over a 2-decade period of laboratory research, clinical trial data, and postmarketing experience. Meanwhile, the real clinical benefits of ESAs have changed very little from those described in the joint American Society of Clinical Oncology/American Society of Hematology guidelines originally published in 2002.[1] Even then, the value of initiation of ESAs was clear only in patients with hemoglobin values < 10 g/dL; quality-of-life measures produced inconsistent and, therefore, clinically inapplicable, results; and ESA use was shown to reduce the proportion of patients requiring red blood cell (RBC) transfusions by approximately 20%. The reality of ESA use that came to light following approval was increased mortality rates in certain populations, higher tumor progression and cancer recurrence rates, and more frequent and severe serious adverse effects including thromboembolism, stroke, and cardiovascular events.

Multiple myeloma remains the second most common hematologic malignancy in the United States, after non-Hodgkin lymphoma.

Anemia is a widely prevalent complication among cancer patients. At the time of diagnosis, 30% to 40% of patients with non-Hodgkin lymphoma or Hodgkin lymphoma and up to 70% of patients with multiple myeloma are anemic; rates are higher among persons with myelodysplastic syndromes. Among patients with solid cancers or lymphomas, up to half develop anemia following chemotherapy. For almost 2 decades, erythropoiesis-stimulating agents (ESAs) were the primary treatment for cancer-related anemia. However, reassessments of benefits and risks of ESAs for cancer-associated anemia have occurred internationally. We reviewed guidelines and notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and chronic kidney disease settings within the United States, Europe, and Canada. In 2008 the US Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to hemoglobin levels < 10 g/dL. In the United States, ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) recommended that ESA benefits do not outweigh risks. In Europe between 2001 and 2006, ESA use increased 51%; since 2006, use decreased by 10%. In 2009, Canadian manufacturers recommended usage based on patient preferences. In Canada in 2007, approximately 20% of anemic cancer patients received ESAs, a 20% increase since 2004. In contrast to Europe, where ESA use has increased over time, reassessments of ESA-associated safety concerns in the United States have resulted in marked decrements in ESA use among cancer patients.

Hematopoietic malignancies account for 6% to 8% of new cancers diagnosed annually. In the year 2009, an estimated 44,790 new cases of leukemia were diagnosed, and 21,870 deaths were attributable to leukemias of all types. The total age-adjusted incidence of leukemia, including both acute and chronic forms, is 9.6 per 100,000 population; the incidence of acute lymphoblastic leukemia (ALL) is 1.5 per 100,000 and of acute myelogenous leukemia (AML) is 2.7 per 100,000 population.

The incidence rates of non-Hodgkin lymphoma (NHL) in the United States have almost doubled between 1970 and 1990, representing one of the largest increases of any cancer. Although the overall incidence rates of NHL began to stabilize in the late 1990s, the temporal trends varied by histologic subtype. Some of this increase may be artifactual, resulting from improved diagnostic techniques and access to medical care, or directly related to the development of NHL in 25- to 54-year-old men with human immunodeficiency virus (HIV) infection. However, additional factors must be responsible for this unexpected increase in frequency of NHL that has been observed throughout the United States.

In 2009 approximately 8,510 new cases of Hodgkin lymphoma (HL) will be diagnosed in the United States. Over the past 4 decades, advances in radiation therapy and the advent of combination chemotherapy have tripled the cure rate of patients with HL. In 2009, more than 80% of all newly diagnosed patients can expect a normal, disease-free life span.

Induction therapy with higher daily doses of daunorubicin improved complete response and boosted overall survival in younger patients with acute myelogenous leukemia, according to results of the phase III ECOG E1900 trial.

Patients with lower-risk myelodysplastic syndromes and anemia can derive long-term benefits from erythropoietin and myeloid growth factor hormones, according to a study in Blood.

Peripheral T-cell lymphomas (PTCLs) are uncommonly encountered malignancies in the United States, and hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and enteropathy-type T-cell lymphoma (ETTCL) are rare subtypes of PTCLs that often present with primarily extranodal disease. Despite the fact that these tumors have distinct clinical and pathologic features, they are often diagnosed after significant delay. The combination of delay in diagnosis with ineffective therapies has resulted in a poor prognosis in most cases. Techniques that identify T-cell receptor gene rearrangements and flow cytometry that can identify characteristic immunophenotypes have guided our understanding of the underlying cell of origin of these rare PTCLs. As knowledge regarding the biology of these lymphomas increases alongside the development of newer therapeutics with novel mechanisms, clinicians must accordingly improve their familiarity with the clinical settings in which these rare malignancies arise as well as the pathologic features that make them unique

Despite the significant progress that has occurred in recent decades in the treatment of many advanced malignancies, skeletal morbidity remains a major problem for patients affected by cancers that metastasize to or grow primarily within bone.[1] Thus as patients with a variety of malignancies survive longer, therapies to limit cancer-associated as well as treatment-associated skeletal complications have become increasingly important for the provision of optimal patient care.

Research presented at the 51st Annual ASH Meeting explored optimal induction therapies for managing multiple myeloma and a potential first-line therapy for patients with non-Hodgkin lymphoma (NHL).

Adult T-cell leukemia/lymphoma (ATL) is defined as a histologically or cytologically proven peripheral T-cell malignancy associated with a retrovirus, human T-cell lymphotropic virus type I (HTLV-1).[1] Southwestern Japan is the district with the highest prevalence of HTLV-1 infection and the highest incidence of ATL in the world. A high prevalence of HTLV-1 infection is also found in the Caribbean islands, tropical Africa, South America, and northern Oceania.

Eltrombopag (Promacta) is the first orally absorbed, small-molecule, thrombopoietin receptor (TPO-R) agonist, approved (on November 20, 2008) by the US Food and Drug Administration (FDA) for the treatment of chronic immune thrombocytopenia (ITP) in patients who have relapsed following treatment with corticosteroids, immunoglobulins, and/or splenectomy.

The purpose of this review is to familiarize oncologists with the clinical and pathologic features of this relatively rare disease spectrum. This should enable appropriate clinical management and reassurance of patients concerned about their prognosis.

One of the greatest challenges facing the physician caring for patients with chronic lymphocytic leukemia (CLL) is the heterogeneity of this disease. Over the past decade, there have been major advances in understanding the pathophysiology of CLL, and in the identification of biomarkers that are helpful to predict the clinical course for individual patients. Over the same period, the available therapeutic options have developed dramatically, exemplified by the introduction of combination therapy with purine analogs and monoclonal antibodies, resulting in significant opportunities to induce complete remission (CR) in CLL patients.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with an extremely variable course. Survival after diagnosis can range from months to decades. As the pathogenesis of the disease is increasingly understood, we begin to unfold the molecular patterns that define the different prognostic subgroups and to develop strategies to predict the clinical course.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western hemisphere. Both the Rai and Binet staging systems have been important clinical tools for predicting outcomes of this heterogeneous disease.

Lymphoblastic lymphoma (LBL) is a rare disease, comprising about 2% of all non-Hodgkin lymphomas (NHLs) in adults.[1] It is a highly aggressive subtype of lymphoma, most commonly of precursor T-cell origin, occurring most frequently in adolescents and young adults, with male predominance and frequent mediastinal, bone marrow, and central nervous system (CNS) involvement.

Lymphoblastic lymphoma (LBL) is a rare disease, most commonly of T-cell origin, that shares biologic features with acute lymphoblastic leukemia (ALL). Indeed, LBL and ALL are considered a single entity (lymphoblastic leukemia/lymphoma, T and B types) in the World Health Organization (WHO) classification of precursor lymphoid neoplasms.

A large, population-based study of the association between venous thromboembolism and mortality in hematologic malignancies found an increased risk of death in patients with acute lymphoblastic leukemia, but not in those with acute myelogenous leukemia. The authors had no explanation for the differential association between the two types of acute leukemia.

In their Areas of Confusion article, “Management of Relapsed Mantle Cell Lymphoma: Still a Treatment Challenge,” Ruan et al attempt to make the case that the relative merits of different upfront approaches for mantle cell lymphoma (MCL) are difficult to appreciate due to the differences in eligible patient populations and limited randomized data.

Dr. Ruan and colleagues provide an excellent summary of available treatment options, as well as new drugs on the horizon, for the management of relapsed mantle cell lymphoma (MCL). As the authors emphasize, treatment of relapsed MCL is strongly influenced by the patient’s first-line therapy and needs to be individualized based on both patient and disease characteristics.

Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma that occurs most commonly in older patients with advanced-stage disease.

On August 22, 2008, the US Food and Drug Administration (FDA) granted marketing approval (licensure) to romiplostim (Nplate, Amgen Inc) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim (Nplate) was the first thrombopoietin (TPO) receptor agonist to receive regulatory approval by the US Food and Drug Administration (FDA) for treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The introduction of mandatory risk evaluation and mitigation strategy (REMS) programs, in which patients must participate in order to receive a new therapy, provides an opportunity to examine an issue affecting ethical oversight and publication of scientific study results.

Drs. Hernandez-Ilizaliturri and Czuczman should be complimented on their comprehensive review of management options for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL).

According to published statistics, in 2008 approximately 66,120 new cases of non-Hodgkin lymphoma (NHL) were diagnosed and 19,160 lymphoma patients died from their disease despite currently available treatment.[1] Diffuse large B-cell lymphoma (DLBCL), the most common type of B-cell NHL, has an aggressive clinical course and, as demonstrated by gene-profiling studies, can be further divided into subgroups with distinct biologic characteristics and prognoses.[2]

Cephalon, Inc, announced that the US Food and Drug Administration (FDA) has approved injectable bendamustine hydrochloride (Treanda) for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab (Rituxan) or a rituximab-containing regimen. The data supporting the FDA approval show that bendamustine is effective, has a tolerable side effect profile in patients with indolent NHL, and that treatment results in a high durable response rate. In March of this year, bendamustine received approval for the treatment of patients with chronic lymphocytic leukemia, the most common form of leukemia in the United States.