Kenneth C. Anderson, MD

ONCOLOGY recently sat down with Kenneth C. Anderson, MD, to discuss the current trends in multiple myeloma treatment, and the explosion of novel therapies that are paving the way to better and more durable outcomes and allowing patients to live longer and more meaningful lives.

This review discusses the clinical presentation; epidemiology; laboratory, radiologic, and pathologic features; and treatment options for each of the heavy chain diseases, emphasising the importance of an accurate pathologic diagnosis and correct interpretation of immunologic studies in their identification.

The real promise of improving patient outcomes in IgD and IgE multiple myeloma lies in multi-drug combinations, next-generation agents, and immunotherapy.

In this interview we discuss the current management and latest treatments and agents in development for multiple myeloma with Dr. Kenneth Anderson of the Dana-Farber Cancer Institute.

Multiple myeloma (MM) is the second most common hematologic malignancy in the United States, affecting slightly more men than women and twice as many African Americans as Caucasians.

Multiple myeloma (MM) is a malignant, progressive plasma cell tumor characterized by overproduction of monoclonal immunoglobulins, osteolytic bone lesions, renal disease, and immunodeficiency.[1] Before the 1980s, patients with MM experienced a slow, progressive decline in quality of life until death approximately 2 years after diagnosis.

Monoclonal gammopathy of undetermined significance (MGUS) is the most prevalent of the plasma cell dyscrasias and is characterized by a low level of production of serum monoclonal (M) protein (classically less than 3 g/dL).

The management of multiple myeloma (MM) has undergone rapid change with the recent emergence of several effective novel agents that have added complexity to individualized treatment decision-making. This paper reviews the initial management of 276 patients with MM diagnosed and treated by 43 US-based community oncologists since January 1, 2008. The case survey data obtained are evaluated within the broad context of published findings from major phase III randomized trials and as such reveal potential education gaps and implications for oncology CME. Overall, the results reveal that most patients were symptomatic at diagnosis and were risk-stratified by fluorescene in situ hybridization (FISH) and/or cytogenetics. When analyzed by age, the overall symptomatology and biomarker-defined risk profiles appeared similar in the three age groups studied (

Responses to treatment of relapsed and refractory multiple myeloma are characteristically short, and median survival is as brief as 6 months. Although prognostic factors in the context of relapsed and refractory disease require further characterization, high-risk patients include those with certain cytogenetic abnormalities, high β2-microglobulin, and low serum albumin.

This is one of a number of studies that show that adding novel drugs to conventional treatments can achieve higher response rates in multiple myeloma,” said Dr. Anderson, who is the Kraft Family Professor of Medicine at the Dana-Farber Cancer Institute in Boston.

Liposomal doxorubicin received FDA approval for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Our better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM—bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM.

In 2004, multiple myeloma was diagnosed in more than 15,000 peoplein the United States and will account for approximately 20% of deathsdue to hematologic malignancies. Although traditional therapies suchas melphalan (Alkeran)/prednisone, combination chemotherapy withVAD (vincristine, doxorubicin [Adriamycin], and dexamethasone), andhigh-dose chemotherapy with stem cell transplantation have shownsome success, median survival remains between 3 to 5 years. Treatmentoptions for patients with multiple myeloma have increased in recentyears, with the promise of improvement in survival. New agents, suchas the proteasome inhibitor bortezomib (Velcade), the antiangiogenicand immunomodulator thalidomide (Thalomid) and its analogs, suchas lenalidomide (Revlimid), together with other small molecules, includingarsenic trioxide (Trisenox), and other targeted therapies, havebeen studied alone and in combination with other antineoplastic therapies,either as induction therapy prior to stem cell transplantation or inpatients with relapsed disease. Bortezomib recently was approved inthe United States for the treatment of multiple myeloma in patientswho have received at least one prior therapy. The use of bortezomibbasedregimens as front-line therapy as well as the use of other agentsin multiple myeloma remain under investigation, and approvals forboth thalidomide and lenalidomide are hoped for soon, with the overallprospect of patient outcome continuing to be increasingly positive.

There was a very rapid response [to CyBorD], which has been typical when you incorporate bortezomib into the initial regimens,” commented Dr. Anderson, from the Dana-Farber Cancer Institute in Boston.