Rethinking CML Care Delivery From Prescription to Persistence

Chronic myeloid leukemia (CML) is a cancer of the blood and bone marrow characterized by the presence of the BCR-ABL fusion gene, which results from a translocation between chromosome 9 (ABL1) and chromosome 22 (BCR), commonly referred to as the Philadelphia chromosome. This fusion gene produces a continuously active tyrosine kinase, which drives the uncontrolled proliferation of white blood cells and underpins the pathophysiology of the disease.

Tyrosine kinase inhibitors (TKIs) are the cornerstone of CML treatment and have well-established clinical benefits spanning the course of a few decades since their introduction to care. At the 2026 Community Oncology Alliance Annual Meeting, experts discussed the treatment landscape for CML, available TKIs, and how to successfully administer these therapies.

CML

CML is most commonly diagnosed in older adults, with a median age at diagnosis in the mid-60s. Many patients are identified incidentally through routine blood work showing abnormal counts, though some may present with symptoms such as fatigue, early satiety due to splenomegaly, unintentional weight loss, or night sweats. The disease progresses through 3 clinical phases: chronic phase, accelerated phase, and blast crisis.

Approximately 90% of patients are diagnosed in the chronic phase, where symptoms are often mild and blood counts—though abnormal—are still manageable. The accelerated phase represents disease progression, while blast crisis resembles an acute leukemia and is associated with significantly worse outcomes. Most clinical decision-making, particularly regarding long-term management, focuses on chronic phase disease.

TKIs

The treatment landscape for CML has been transformed by TKIs, which specifically target the BCR-ABL protein. Imatinib (Gleevec; Novartis), a first-generation TKI, was the first to revolutionize care, turning CML from a fatal disease into a chronic, manageable condition for most patients. It remains a preferred option for older patients or those with significant comorbidities, where tolerability and overall survival (OS) are the primary goals.

Second-generation TKIs, including dasatinib (Sprycel; Bristol Myers Squibb), nilotinib (Tasigna; Novartis), and bosutinib (Bosulif; Pfizer Inc), are more potent and can achieve deeper and faster molecular responses. These agents are often considered when the goal is treatment-free remission, although each has distinct toxicity considerations, such as pleural effusion with dasatinib or vascular and metabolic risks with nilotinib.

Third-generation TKIs, most notably ponatinib (Iclusig; Takeda Pharmaceutical Company), play a critical role in patients with resistant disease, particularly those harboring the T315I mutation, which confers resistance to many earlier-generation agents. However, ponatinib is associated with significant vascular risks and requires careful patient selection and monitoring.

More recently, allosteric inhibitors have emerged as an alternative approach, targeting a different binding site on the BCR-ABL protein rather than the adenosine triphosphate-binding site. These agents offer additional options for patients with resistant mutations or intolerance to other therapies.

Treatment goals in CML generally fall into 2 broad categories. The first is optimizing OS, which can often be achieved by maintaining BCR-ABL levels below 1%, corresponding to a major cytogenetic response. The second goal is achieving treatment-free remission (TFR), which requires a deeper molecular response—typically MR4 or better, corresponding to BCR-ABL levels of 0.01% or lower on the International Scale.

Adverse Effect Management and Monitoring for TKIs

TKIs are associated with various adverse effects (AEs)—some of which are observed across agents and others that are more specific. Myelosuppression, or low blood counts, is common and can manifest as anemia, neutropenia, and thrombocytopenia. Clinically, these changes carry important risks: neutropenia increases susceptibility to infections, thrombocytopenia raises the risk of bleeding and bruising, and anemia can contribute to fatigue and decreased quality of life.

Management typically involves close monitoring with frequent complete blood counts, especially early in treatment, with intervals extended once stability is achieved. For more severe cases—such as grade 3 or 4 cytopenias—temporary dose holds or dose reductions may be necessary. Supportive care, including blood transfusions, may be used when indicated.

Gastrointestinal symptoms are also frequently observed, particularly with agents such as imatinib and bosutinib, where diarrhea and nausea are common. These symptoms can often be managed with supportive care strategies. Patients may benefit from taking their medication with food and adequate hydration, if permitted by the prescribing information. Antiemetics such as ondansetron can help control nausea, while loperamide is commonly used for diarrhea. Dietary adjustments and maintaining proper hydration are also important. In cases where symptoms are severe or persistent despite these interventions, dose modification or switching to an alternative TKI may be necessary.

Edema and fluid retention represent another class of side effects that can impact patients on TKI therapy. These may present as periorbital swelling, peripheral edema, or weight gain, and in some cases, more serious complications such as pleural effusions may occur depending on the specific agent. Management includes conservative measures such as salt restriction and leg elevation, along with pharmacologic interventions like diuretics (eg, furosemide). It is also important to evaluate for underlying cardiac or renal dysfunction that could contribute to fluid retention

Dermatologic toxicities, including rash and other skin reactions, are also relatively common. Patients may develop maculopapular rashes, pruritus, or skin dryness. Initial management focuses on supportive care, including the use of moisturizers, avoidance of hot showers, and gentle skin care products. Topical corticosteroids and antihistamines can be helpful for managing inflammation and itching. In more extensive or severe cases, a short course of systemic steroids may be required, along with dose adjustments. If skin reactions are recurrent or intolerable, transitioning to an alternative TKI may be considered.

Operationalizing TKIs and the Pharmacist’s Role

Establishing a structured workflow is essential to ensuring that every patient with CML receives the most appropriate TKI, along with safe monitoring and ongoing adherence support. A key component of this approach is centralized prescription handling. In this model, all oral oncolytic prescriptions—including TKIs—are routed through an in-house retail or specialty pharmacy rather than being sent directly to an external pharmacy. This creates a critical checkpoint before prior authorization (PA) is initiated, allowing the care team to confirm that the selected therapy, dosing, and monitoring plan are appropriate from the outset.

Within this workflow, pharmacist oversight plays a central role. Before a PA is submitted, pharmacy technicians route each new TKI prescription to a pharmacist for review. The pharmacist verifies that the chosen agent aligns with the patient’s disease characteristics, including disease phase, mutation status (such as the presence of T315I), and prior lines of therapy. They also ensure that appropriate baseline assessments have been completed, such as laboratory testing and electrocardiograms (EKGs) for agents associated with QT prolongation or vascular risk, like nilotinib or ponatinib. In addition, the pharmacist screens for potential drug–drug interactions and contraindications, including proton pump inhibitors, QT-prolonging medications, strong CYP3A4 modulators, and certain cardiac therapies.

This upfront validation is designed to avoid downstream complications. Without it, errors or omissions may only become apparent after PA approval—such as selecting a TKI that is not optimal for a patient’s comorbidities or failing to complete necessary baseline testing. In these cases, the process must be restarted, requiring cancellation of the original authorization and submission of a new request, ultimately delaying treatment. A structured workflow helps prevent these inefficiencies and ensures a smoother path to therapy initiation.

Beyond initial prescribing, embedding safety and adherence checks throughout the patient journey is equally important. Providers routinely conduct comprehensive baseline assessments, including evaluation of cardiovascular history, pulmonary conditions relevant to specific TKIs, metabolic status, and liver and kidney function. A complete medication and supplement review is also necessary to identify potential interactions.

Ongoing monitoring is a continuous process that includes both clinical and molecular assessments. Patients typically undergo regular BCR-ABL PCR testing—often every 3 months early in treatment—to evaluate molecular response. Laboratory monitoring may include complete blood counts, comprehensive metabolic panels, lipid levels, glucose, and EKGs when clinically indicated. Importantly, toxicity and adherence are assessed at multiple touchpoints, including in-person visits, pharmacy refill interactions, and remote check-ins through digital health platforms.

A critical insight from clinical practice is that so-called “mild to moderate” adverse effects—such as chronic diarrhea, rash, or fatigue—are a common reason patients discontinue TKIs without explicitly reporting issues. To address this, care teams proactively ask about missed doses and side effects at every interaction. Early intervention, whether through supportive medications, dose adjustments, or patient education, helps mitigate these issues and supports sustained adherence, which is essential for achieving optimal long-term outcomes in CML.

REFERENCE

Morse A. Advancing Pharmacist-Led Care in CML: Bridging Knowledge and Practice Gaps to Optimize TKI Management and Patient Adherence. Presented at: 2026 COA Annual Meeting. April 28-29, 2026. Orlando, FL.