NASP Session Explores FDA-Approved Treatment Options for AML, MM

In "2019 State of Care: Oncology/ Hematology,” during the National Association of Specialty Pharmacy 2019 Annual Meeting and Expo in Washington, DC, Joseph Barone, PharmD, BCOP, examined current standards of care for acute myeloid leukemia (AML) and multiple myeloma (MM) and identified new agents approved over the past year.

ACUTE MYELOID LEUKEMIA

Barone, director of clinical oncology services at Onco360 Oncology Pharmacy in Louisville, Kentucky, noted that AML is a hematologic malignancy characterized by clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and other areas. It is the most common form of acute leukemia in adult patients and can quickly become fatal without prompt treatment. Risk factors include prolonged exposures to petrochemicals, prior receipt of cytotoxic chemotherapy, or precursory conditions that may evolve into AML. Approximately 21,000 new cases of AML are diagnosed each year, and there are approximately 10,000 deaths, according to Barone.

“While 58% of patients who are diagnosed with AML are over age 65 at the point of initial diagnosis—or a large [part of the] Medicare population—about 72% of those patients over 65 die. So, you are dealing with a disparity of survivability in the disease state as a function of increasing age,” Barone explained.

There are 2 forms of treatment for AML: induction therapy for complete remission (CR) and consolidation therapy to maintain CR. CR is defined as having less than 5% of myeloid blasts present in the bone marrow, coupled with an absolute neutrophil count greater than 1000. The traditional regimen for induction chemotherapy, irrespective of favorable intermediate or unfavorable-risk AML, is the 7+3 regimen. Standard dosage of cytarabine is given on a consistent basis for 7 days and then an anthracycline drug, such as daunorubicin or idarubicin, is administered for 3 days. Historical CR rates produced by this regimen are 60% to 80% in patients younger than 60 years; there is a drop off in CR for patients older than 60 years.

After induction therapy, a patient is given consolidation therapy done with high-dose cytarabine. The standard dosage for cytarabine of 200 mg/m2 /day. In the high-dose regimen, cytarabine is given at 3 g/ m2 every 12 hours for 3 days of each cycle. Patients receive 3 to 4 cycles of a given consolidation regimen. Patients and those who have favorable-risk AML will get 3 to 4 cycles of high-dose cytarabine. If patients remain in remission after these treatment cycles, they will no longer receive treatment.

Barone also examined 3 FDA-approved medications for AML:

• Ivosidenib (Tibsovo) for the treatment of AML with a susceptible IDH1 mutation as detected by an FDAapproved test in patients 75 years or older.
• Glasdegib (Daurismo) for the treatment of AML in patients with newly diagnosed disease.
• Gilteritinib (Xospata) for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation as detected by an FDA-approved test.

MULTIPLE MYELOMA

MM is a hematologic malignancy involving plasma cells that accumulate in the bone marrow, leading to bone destruction and marrow failure. It occurs when cancerous plasma cells produce an abnormal protein referred to as a monoclonal protein (M-protein). There are 2 types of myeloma: smoldering or asymptomatic. Smoldering is characterized by the presence of M-protein (>3 g/dL); however, it does not cause any symptoms or organ/tissue impairment. Symptomatic myeloma involves clonal bone marrow plasma cell of at least 10% plus any of the CRAB criteria (calcium level [ie, hypercalcemia], renal failure, anemia, bone lesions).

MM treatment involves triplet therapy of lenalidomide (Revlimid), bortezomib (Velcade), and a 4-6 cycle regimen of dexamethasone. CR is achieved when the M-protein has vanished and there is less than 5% of plasma cells within the bone marrow.

Barone concluded by discussing a medication recently approved by the FDA, selinexor (Xpovio). The drug, in combination with dexamethasone, is used for the treatment of adult patients with relapsed or refractory MM who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.