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Expert Answers to FAQ on CML
Expert Answers to Frequently Asked Questions About Chronic Myeloid Leukemia

Released: October 22, 2025

Michael J. Mauro
Michael J. Mauro, MD
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Key Takeaways
  • Selection of TKI treatment for CP-CML should balance efficacy, cost, comorbidities, and patient preferences.
  • Treatment-free remission is a realistic goal for eligible patients and represents functional cure of CP-CML.

I recently gave several presentations as part of a larger educational series where I discussed the latest data and guidelines for treating patients with chronic-phase chronic myeloid leukemia (CP-CML), including how to monitor patients during treatment, pursuing treatment-free remission (TFR), and how to sequence therapies to prevent resistance and progression. Here I share my answers to frequently asked questions during this series.

What TKIs are currently approved by the FDA for CP-CML?
Starting in 2001, we have had a sequence of approvals in CML, and I think we will see more approvals in the near future. Imatinib was the first TKI targeting the BCR::ABL1 fusion protein to be approved by the FDA for this disease, initially in the second line after interferon-α therapy and subsequently for frontline use in Philadelphia chromosome–positive (Ph+) CP-CML.

The next agent approved was dasatinib, which was initially tested in the setting of resistance or intolerance to imatinib. Dasatinib is now indicated for newly diagnosed adult patients with CP-CML and for patients with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML. It is also incorporated into the treatment for Ph+ acute lymphoblastic leukemia (ALL).

Nilotinib is another second-generation TKI that was also tested in a similar fashion to dasatinib. It is approved for newly diagnosed Ph+ CP-CML and both CP-CML and accelerated-phase (AP) CML after resistance or intolerance to prior therapy that included imatinib.

Bosutinib was the last of the second-generation TKIs to be approved for CP-CML for all lines of therapy.

Ponatinib and asciminib are both considered third-generation TKIs. Ponatinib was developed to combat TKI resistance associated with the T315I mutation that we see across all phases of Ph+ leukemia. It is also well incorporated into the treatment landscape for AP-CML, blast-phase (BP) CML and Ph+ ALL.

Finally, asciminib is the latest agent approved for CP-CML. Unlike the other approved TKIs, it is a specifically targeting the ABL myristoyl pocket (STAMP) inhibitor. This unique mechanism of activity translates to greater comparative efficacy, the potential for use in combination with prior approved TKIs which target the ATP binding pocket (‘active site’), activity against mutations including the T315I variant, and a distinct and limited mechanism of resistance. In 2021, asciminib was approved for Ph+ CP-CML in the third line after previous treatment with 2 or more TKIs, based on the ASCEMBL trial comparing asciminib and bosutinib, and for adults with Ph+ CP-CML and T315I mutations. In October 2024, it received accelerated approval for frontline use for adults with newly diagnosed Ph+ CP-CML, based on the ASC4FRIST study demonstrating superior efficacy and improved safety compared to other investigator-selected frontline TKIs.

Does cost play a role in your treatment decisions?
It certainly does. Treatment is only successful if patients have easy long-term access to a therapy that is effective for them. For that reason, I would not discourage patients from using lower-cost generic drugs. For instance, imatinib may not be the optimal treatment for most patients, but it is still very effective and widely available in generic form at a low cost. Dasatinib is also available as a generic, has improved efficacy compared with imatinib, and has a flexible dosing schedule, which is a great benefit to patients. However, newer agents can offer an advantage if they are feasible and accessible to the patient. Further study of long-term benefits and potential for functional cure (successful TFR) will help better define the benefits of newer TKIs. Some of these agents have patient assistance programs to help improve accessibility. The good news is that as new treatments have been developed for CML, the older agents still remain good options.

How do comorbidities like cardiovascular disease and diabetes influence TKI selection?
Nilotinib and ponatinib are the agents we see have the highest risk of vascular events, including arterial occlusive complications. In addition, nilotinib is associated with worsening of hyperglycemia. However, studies to date suggest all TKIs, with the exception of imatinib, likely have some impact on cardiovascular health, so I would recommend to any patient receiving a TKI long-term to be managed properly to mitigate risk factors such as hypertension, diabetes, and lipid disorders as well as encourage lifestyle changes including tobacco cessation and maintaining proper weight. I prefer my patients to be very closely followed by their primary care team, and in many instances cardiology or even cardio-oncology specialists, to optimize cardiovascular health long term.

Are patients being treated with imatinib for many years experiencing any long-term adverse effects?
Imatinib, studied the longest of any TKI, does seem to affect renal function and is associated with decreased glomerular filtration rate and increased creatinine clearance rate; bosutinib also may elicit the same changes. However, some of these effects may be attributable to an artifact in the way these values are measured in the presence of the TKIs and may not represent intrinsic renal damage. We do see some improvement in measured renal function when patients ultimately stop treatment and we do not see progressive renal decline. Ultimately, I think we need to further study long-term treatment outcomes and late effects as more patients are remaining on treatment for many years, some lifelong, and TFR offers the opportunity to examine post-treatment survivorship.

How do you manage imatinib-induced generalized edema and/or periorbital edema?
For TKI-associated edema, principles of management include salt limitation and adequate treatment of high blood pressure and other comorbidities. Imatinib can result in significant periorbital edema that is primarily cosmetic in nature and does not usually affect vision, but it can be a burdensome adverse effect for patients. Cosmetic remedies can be tried including over-the-counter phenylephrine hydrochloride and cold compresses. Low-dose thiazide diuretics can also be considered for periorbital edema but may be more effective and indicated for generalized edema.

When do you consider TFR?
The NCCN guidelines list a set of criteria defining successful treatment that is amenable to attempt TFR with careful, prescribed observation after TKI discontinuation. Patients must be adults with CP-CML and no history of AP-CML or BP-CML. They need to have at least 3 years of treatment and a history of measurable BCR::ABL1. Finally—and of most importance—they need to have a stable deep molecular response that is defined as BCR::ABL1 levels below 0.01% for at least 2 years on at least 4 separate molecular assays (≥3 months apart). If a patient meets these criteria, we can offer this option if there is no threat from adverse effects, but TFR is not an expectation. For instance, if a patient meets these criteria and is tolerating imatinib, there is generally no harm in continuing treatment. Conversely, a young female diagnosed with CML who wants to have a child may represent a scenario where planning for treatment discontinuation may be a strong goal. I will say that it is very satisfying to help patients discontinue treatment, facilitate patients’ goals regarding pregnancy and family planning, and reassure newly diagnosed patients that they have a highly treatable and possibly functionally curable form of leukemia.

Is CP-CML considered a curable disease?
Yes; long-term follow-up of patients after TFR living with no therapy and no evidence of disease for many years, and increasing numbers of patients eligible for and proceeding into TFR means we are curing patients with CP-CML. This disease is intriguing because some patients in remission continue to have polymerase chain reaction (PCR) tests that are positive for BCR::ABL1 at very low levels. Research has suggested this may be linked to long-lived non-myeloid B-cells and T-cells that were part of the original clonal expansion at disease inception and will not cause disease recurrence.

How often do you bring patients back for follow-up during TFR?
As outlined in the NCCN guidelines, for the first 6 months, we do monthly molecular monitoring followed by monitoring every 2 months for the next 6 months. Both the NCCN and European guidelines require continued monitoring every 3 months indefinitely, even beyond 5 years of TFR. Currently, we continue to gather further data to guide any potential further tapering of long-term monitoring after TFR and to determine if halting monitoring would be feasible. However, I anticipate guidelines will change in the future to reduce the monitoring frequency.

How many of your patients do you refer to allogeneic stem cell transplant?
In my clinic, I currently care for a large number of patients (>600) with CML and at any time there may be 1 rare patient proceeding towards or undergoing transplant. These patients may have rare challenges such as CML with P190 fusion, which presents higher risk, with intolerance after imatinib and asciminib and intolerance with ponatinib who progress to lymphoid blast crisis. Patients with blast phase progression are generally advised to proceed to transplant, so my patient with this history did so, achieved remission with chemotherapy, and is now doing well. Another example is a case of mine of CP-CML with PCR testing showing BCR::ABL1 levels of 40% despite multiple lines of therapy, including asciminib.

Your Thoughts
What TKIs do you typically use in your clinical practice? Have you had success assisting patients in pursuing TFR? Tell us about your experience in the discussion section below.

Join us in-person in Orlando or virtually on December 5, 2025, for our symposium on CP-CML with Jerald Radich, MD; Neil P. Shah, MD, PhD; and B. Douglas Smith, MD, to gain more insights and the latest information on the management of patients with this disease!

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Which TKIs are you using for your patients with newly diagnosed CP-CML? (Select all that apply.)

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