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AML Therapy for Unfit Patients
A Nurse’s Perspective on Managing AML in Unfit Patients

Released: January 13, 2022

Expiration: January 12, 2023

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Acute myeloid leukemia (AML) is an aggressive blood cancer that affects older individuals, and the median age of diagnosis is 68 years. AML is diverse disease with different karyotypes and mutations that affect patient outcomes. Treatment decisions for AML are largely dependent on patient and disease characteristics that determine whether patients are eligible for intensive induction chemotherapy, potentially followed by a hematopoietic stem cell transplant. Unfortunately, many patients diagnosed with AML are unfit for intensive induction chemotherapy. Therapies for those patients will be the focus of this commentary, along with a discussion of the role nurses play in managing patients with AML.

Determining Patient Fitness for AML Treatment
Fitness for intensive chemotherapy is determined by a patients’ performance status, physical function, and cytogenetic profile. A fit adult has good performance status and physical function, meaning they are able to do most of their activities of daily living on their own without any assistance. Unfit patients are those with several comorbidities that interfere with daily living and a poor performance status. Cytogenetics also play a role in therapy selection, and patients with abnormal cytogenetics may respond poorly to available treatment options.

Treatment Goals in Patients Unfit for Intensive Therapies
Treatment goals for patients with AML who are unfit for intensive chemotherapy may be different than for patients who are eligible for intensive therapy. Treatment goals may include maintaining or improving blood counts, reducing transfusion dependence, and stabilizing disease. Strategies to minimize and manage ongoing symptoms related to myelosuppression and chemotherapy adverse events need to be considered. Patients may become deconditioned over time due to a large amount of time spent in bed, and we may discuss how to improve their physical function. Ongoing discussions with patients and their families are important to establish goals and what quality of life means to each patient. A focus on shared treatment decision-making with the patient helps ensure that their needs are being met.

Therapeutic Options in AML
Less-intensive therapy is a suitable treatment option for older adults with AML and poor performance status. The cure rate with chemotherapy is low in individuals older than 60 years of age, and the median survival is 6‑10 months. Treatment options include low‑dose cytarabine (LDAC) or hypomethylating agents (HMA) such as azacitidine or decitabine. Other treatment options include combinations with venetoclax, a BCL2 inhibitor. Venetoclax is administered orally and approved by the FDA for use in combination with azacitidine, decitabine, or LDAC to treat adults with newly diagnosed AML who are 75 years of age or older or those with comorbidities that prevent the use of standard intensive induction therapy.

Venetoclax Combinations in AML
The phase III VIALE A trial demonstrated that the combination of venetoclax plus azacitidine resulted in a significantly better median overall survival compared with azacitidine plus placebo in treatment-naive patients with AML who were ineligible for standard induction therapy. Grade ≥3 cytopenias and any-grade nausea and infections were more common in the venetoclax plus azacitidine arm than in the placebo plus azacitidine arm.

In the phase III VIALE-C trial, venetoclax plus LDAC yielded a longer overall survival compared with LDAC plus placebo in patients with previously untreated AML who were ineligible for induction chemotherapy due to age (75 years or older) or comorbidities.

Venetoclax Dosing and Drug Interactions
Per the package insert, dosing of venetoclax includes a ramp-up of 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 in conjunction with an HMA. For patients receiving venetoclax plus LDAC, ramp-up adds a 600 mg dose on Day 4. Patients should be directed to take venetoclax with food and water at approximately the same time of day and swallow the pill whole without crushing or breaking it first. Patients receiving venetoclax are typically treated until disease progression or unacceptable toxicity.

There are some drug–drug interactions to be aware of with venetoclax. With concomitant use of moderate or strong CYP3A4 inhibitors, venetoclax dose should be reduced by 50% or 75%, respectively. Concomitant use of venetoclax and CYP3A4 inducers is not advised, and alternatives should be used.

Venetoclax and Tumor Lysis Syndrome
The incidence of tumor lysis syndrome (TLS) among patients with AML who are receiving venetoclax is low, unlike for other diseases, but it is important to take measures to prevent and assess patients for TLS at each encounter. Signs of TLS include elevated uric acid, potassium, and phosphorus levels; increasing creatinine levels; and a decreased calcium level. Notable risk factors for TLS include circulating blasts, high burden of leukemia involvement in bone marrow, elevated pretreatment lactate dehydrogenase, or reduced renal function. To minimize the risk for TLS, a baseline-level white blood cell count should be <25 x 109/L prior to initiation of venetoclax. It is also important that patients have prophylactic hydration and antihyperuricemic medications such as allopurinol available to reduce the risk of TLS and then continue through the venetoclax ramp‑up phase. Blood chemistries should be monitored prior to dosing, 6-8 hours after each new dose during ramp-up, and 24 hours after reaching the final dose. For patients at risk for TLS, increased laboratory monitoring is important, and dosage of venetoclax may need to be adjusted. 

The Role of Nurses in Managing Adverse Events
AML is associated with myelosuppression and fatigue, which may be intensified by some therapies. A common adverse event of AML therapy is gastrointestinal toxicities. Nausea, vomiting, and upset stomach can be managed with anti-nausea medications. Patients may be advised to eat small meals and to take their medication at least 30 minutes to 1 hour before eating. Reducing spicy foods may also help mitigate gastrointestinal symptoms. Neutropenia is common and increases the risk of infection, so nurses remind patients of the importance of hand hygiene. Patients should also wear a mask and avoid people who are sick. Patients with anemia often feel better once they receive a red blood cell transfusion. For patients with thrombocytopenia, we can minimize the risk of bleeding by avoiding extra blood draws and by advising them to not engage in any vigorous activities. Fatigue is a common problem for patients with AML, and this may be increased by some therapies. We work with both the patient and their family to identify and improve fatigue. Recommendations include clustering care and activities throughout the day. Physical activity is the most effective way to manage fatigue, and this can be walking outside—potentially to the mailbox if it is fairly close—just so the patient is able to move their body. Nurses also discuss with our patients the impact that fatigue has on daily and social activities, which can impact quality of life, because we know that often patients are not able to enjoy as many activities as they did before diagnosis and therapy.

The Role of Nurses in Promoting Adherence
Poor adherence to treatment is a common issue for patients receiving oral medicines including venetoclax. My colleagues and I conducted a focus-group study with adults with AML that identified barriers to adherence. We focused on 3 main themes related to adherence to oral medications: medication adherence challenges, managing an oral adherence plan, and strategies to improve oral adherence. Participants in the study mentioned that writing down schedules, taking medications around meals, and using a pillbox or reminders such as alarms all were helpful for them.

In a mixed methods study with 3 geographical sites, we collected survey data from 100 patients with AML and identified common challenges to oral adherence. The most troublesome challenge was the number of pills that patients were taking. In addition to pills for AML, patients were receiving other medications for their comorbidities. Adverse events also impacted adherence. Loss of appetite was common and considered the most problematic adverse event. Patients with a loss of appetite may be less likely to take their medication or pick and choose which medication to take that day. Incorporating their medication into their daily routine improved oral adherence. For example, when patients think about their morning routine, if they watch a TV show or have a phone call every day around the same time, they can take their medication at that time. Survey results also showed that patients considered their healthcare team the best source of information. All these things are important to keep in mind as we work to overcome the barriers to adherence we often see in patients with AML. At each patient encounter, it is suggested that nurses ask patients about their adherence to their medications and reasons for nonadherence.

Addressing Other Patient Needs
As nurses, it is important to manage both the physical and psychological symptoms of our patients with AML. Patients face different barriers and challenges. It is important to assess barriers to transportation or finances that may limit a patient’s ability to travel to the clinical or hospital for follow-up visits. Psychological symptoms such as anxiety, depressive symptoms, distress, and posttraumatic stress disorder are experienced by patients with AML during their treatment. Offering additional psychological supports such as cognitive behavioral therapy or mindfulness-based interventions are potential strategies to improve psychological health and well-being. We also need to focus on interdisciplinary collaboration, which is critical as we work with pharmacists, social workers, spiritual care, and others to ensure that the patients’ needs are being met.

Your Thoughts?
What factors do you take into consideration when deciding on a treatment for your patients with AML who are unfit for intensive therapy? Answer the polling question and join the conversation by posting a comment in the discussion section.

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