Considerations in the Treatment of Acute Myeloid Leukemia

ACUTE MYELOID LEUKEMIA (AML) is the most frequently occurring cause of acute leukemia in adults. This aggressive form of cancer is diagnosed in approximately 21,000 individuals annually in the United States and slightly more than half will die each year. In a Pharmacy Times®Practice Pearls video series, experts discussed best practices in the management of AML, including patient identification, formulary decisions, and providing therapy from an outpatient setting for optimal patient care.

The panelists—Katie Culos, PharmD, BCOP, a hematology/oncology clinical pharmacist at Vanderbilt University Medical Center in Nashville, Tennessee; Amanda Brahim, PharmD, BCOP, BCPS, BCACP, a hematology/oncology clinical pharmacist at Memorial Cancer Institute in Pembroke Pines, Florida; and Yehuda Deutsch, MD, a hematologist/oncologist in the Department of Malignant Hematology and Cellular Therapy at Memorial Cancer Institute—noted that myriad factors are involved in determining the appropriate care pathway for patients with AML.

Deutsch said that the median age of onset for AML is 65 years, and treatment outcomes are progressively worse as the patient ages. It appears that risk is elevated if patients have had antecedent hematologic malignancies, environmental exposures to carcinogens, or previous chemotherapy, radiation, or immunosuppressant therapy.

“AML is associated with specific chromosomal abnormalities,” Deutsch said. “These include translocations, rearrangements, deletions, or gains in parts of chromosomes, as well as specific mutations in regulation of cell growth and differentiation.”

In diagnosing patients with AML, Brahim noted that they often present with signs and symptoms of anemia, such as shortness of breath, weakness, and easier bruising and bleeding, as well as fatigue that may have been present for weeks or months.

The course of treatment is determined by whether a patient has a new diagnosis or if the disease is recurrent or relapsed.

“If patients are determined to be candidates for intensive chemotherapy, they are given intensive chemotherapy over 5 to 7 days, usually in the hospital,” Deutsch said. “The goal of this therapy is to induce remission. However, if left untreated after being in remission, the leukemia most likely will relapse. Therefore, patients need to continue on therapy with something called postremission therapy.”

“At times, patients are referred to us when certain tests have not been done...and [even when they have been done,] sometimes we will repeat them to make sure that we have the correct information, so we can make the right decision for treatment,” Deutsch said.

He added that the additional testing conducted by Memorial Cancer Institute allows the care team to better develop an optimal treatment plan for a patient. Because of the importance of the cytogenetic and molecular mutations in the diagnosis of AML, it is vital that these tests be performed before treatment begins. The cytogenetic and molecular samples are collected with bone marrow biopsy and aspiration. Should providers be unable to collect samples through these methods, they can do so through the peripheral blood. Cytogenetic analysis or chromosomal analysis must be completed, as must molecular testing with next-generation sequencing or polymerase chain reaction.

“We typically collect these specimens, in terms of molecular testing. It’s really important to have testing for those mutations that are prognostic, predictive biomarkers, and can be targeted,” Deutsch said.

Although patients with AML need treatment quickly, Deutsch explained that physicians often wait for the results of the tests before starting treatment. The return of some test results, such as multiple-gene sequencing panels, can take a week or even longer. Additionally, age, fitness, disease-related factors, and comorbidities are always taken into account when treatment decisions are made, especially for older patients who may have more comorbidities and who may not be able to tolerate intensive induction chemotherapy.

“Patients older than 75 years who are less fit and have more comorbidities are not [generally] candidates for induction chemotherapy. However, those [factors] do not absolutely exclude them,” Deutsch said. “Patients who are in their 60s or 70s are in a gray zone, where we have to take into account their comorbidities.”

Over the past few years, a number of targeted agents have been approved for AML.

According to Brahim, “As pharmacists, we have so many drugs in our armamentarium. When we get the results back for cytogenetics [and] specific mutations, we use those prior to rounds to come up with an appropriate treatment recommendation.”

“We added gemtuzumab ozogamicin when it came back to the market. We added [cytarabine and daunorubicin (CPX-351)] when it came to the market,” Brahim said. “We also have midostaurin (Rydapt), which we are starting on the inpatient side for those patients who are getting traditional 7+3 [chemo-therapy] but have an FLT3 mutation.”

Deutsch added that when a desired drug, such as an isocitrate dehydrogenase (IDH) inhibitor, isn’t on formulary, there is significant support from both the inpatient and outpatient pharmacies, patient assistance programs, and specialty pharmacies to help patients access the medications, even when they are admitted to the hospital.

In addition, Brahim said that venetoclax (Venclexta) is stocked in the hospital along with midostaurin, since the staff has recognized that some patients may have an urgent need to start therapy immediately. Going through a traditional specialty pharmacy route, these drugs may take up to 2 weeks to reach patients, so the treatments have become an unofficial part of Memorial Cancer Institute’s inpatient formulary.

For a home supply of other targeted agents that aren’t on the formulary, Brahim noted that the hospital generally has a fully integrated system of IDH inhibitors.

“We have our specialty pharmacy within our health care system, so generally we’ll process their prescriptions through there, then treat them as a patient’s own medication,” she explained. “If it’s truly necessary and urgent, and we are not able to fill those on the outpatient side, we will obtain them on a case-by-case basis for our patients.”

“Patients are so much happier sleeping at home,” Deutsch said. “When they’re home, they can sleep in their bed, they don’t have to be awakened constantly throughout the night, and they’re definitely much happier.”

According to Brahim, traditional 7+3 chemotherapy is still entirely inpatient at Memorial Cancer Institute. Patients receiving CPX-351 can either be inpatient or outpatient, depending on the individual patient’s strength. Brahim said the hospital uses a set of rooms in the inpatient/outpatient unit, which is located on the inpatient side of the hospital but used for outpatient treatments.

“We generally have used that area for patients who are immediately post transplant, posthospital discharge for transplant. But we also use it in the setting of intensive chemotherapy,” Brahim said.

Finally, patients receiving some newer oral agents are generally prescribed in an outpatient setting. These include venetoclax and some IDH inhibitors.

The novel option to prescribe CPX-351 in an outpatient setting has greatly changed treatment for AML, Deutsch said. At his institution, Deutsch said physicians have begun slightly delaying treatment while waiting for cytogenetic and molecular results in order to determine the appropriate treatment.

“We realized it’s safe to do that, [and] some clinical trials have shown that,” Deutsch said. “We see that our patients sometimes are sitting and waiting for these results and they’re well and stable.”

A second factor of the novel treatment option is that, in contrast to other therapies such as traditional 7+3 chemotherapy, CPX-351 does not require constant infusions, according to the panel. Without the need to be in a hospital setting, therefore, patients can stay at home more frequently while still receiving treatment.

The inpatient/outpatient facility is a key to being able to provide care in both environments, the panelists said. Deutsch said Memorial Cancer Institute has approximately 16 beds and infusion suite chairs in the facility. Most of the nurses are outpatient nurses, although they do have experience in inpatient care. Deutsch added that the unit has a dedicated nurse practitioner, in addition to the physician on inpatient service.

“Many of these patients will have fevers, and many of them will have to get admitted to the hospital, but they’re basically already in the hospital,” Deutsch said. “They can be directly admitted—we can have hospitalists come and see them, sometimes other specialists, and any scans or tests that need to be done can be done immediately there.”

Finally, Brahim said treatment for AML in both the inpatient and outpatient setting provides many opportunities for pharmacists to have a positive impact on outcomes.

“I think it’s actually a great opportunity for a pharmacist to be involved and to really shift the focus to practicing patient- and family-centered care, where the patient and their caregivers are at the center of it all and we help them, educate them, and really try to do our best to support them from the outpatient perspective,” Brahim concluded.