eCase - Chronic Myeloid Leukemia Treatment

CME

Chronic Myeloid Leukemia: Optimizing Use of TKIs to Individualize Treatment Across the Disease Spectrum

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: August 15, 2024

Expiration: February 14, 2025

Fadi Haddad, MD

CME/CE Information

Activity

Progress

1 2

Course Completed

BACK | NEXT

Introduction Overview of CML Personalized Initial Therapy for A Young Patient with Newly Diagnosed CML and a Goal of TFR Personalized Initial Therapy for an Older Patient With Newly Diagnosed CML and Multiple Comorbidities Personalizing Therapy for Patients With Intolerance to Initial Therapy Personalizing Therapy for Patients with Suboptimal Response to Initial Therapy Personalizing Therapy for Patients with Loss of Response to Previous TKI Therapy Concluding Thoughts References

Summary: The State of CML Treatment in 2024

In 2024, CML treatment primarily involves targeted therapies, particularly TKIs, which have revolutionized management of the disease. For frontline therapy, the choices of TKI include imatinib, dasatinib, bosutinib, and nilotinib. The choice of frontline agent can depend on the goal of treatment (survival or TFR), patient comorbidities, comedications, CML risk category, and cost.² If frontline therapy fails, it is important to reassess the treatment strategy and determine whether failure is due to nonadherence, treatment toxicities, or disease resistance. For many patients whose waning response is due to nonadherence because of treatment-related AEs, dose reductions of TKIs are an excellent approach that can help maintain efficacy and improve tolerability.

Resistance to frontline therapy should be confirmed with molecular monitoring that shows a clear loss of response and a mutation analysis. Choice of later-line TKI therapies is then based on mutation profile and TKI side effect profiles together with any relevant patient comorbidities. Dasatinib, nilotinib, or bosutinib are reasonable choices if resistance to frontline imatinib or frontline second-generation TKIs is identified, tailored to the patient’s comorbidities and ABL1 mutational status. Ponatinib has demonstrated efficacy against the T315I mutation and other resistance mutations. The STAMP inhibitor asciminib has demonstrated efficacy in resistant CML and provides an option with a novel mechanism of action. Regular monitoring and personalized treatment adjustments are crucial for optimizing outcomes in patients with resistant CML.

The recent results from the ASC4FIRST trial demonstrated the superiority of asciminib over imatinib and second-generation TKIs in the frontline setting of patients with chronic-phase CML, with higher MMR rates at 48 weeks. These positive results may lead to the approval of asciminib for use in patients with newly diagnosed CML. However, with the availability of generic imatinib and soon second-generation generic TKIs, the price of asciminib is a significant consideration and barrier to its use in the frontline setting. Furthermore, long-term safety data need to be established for asciminib before it can replace first- or second-generation TKIs in patients with newly diagnosed CML. Previously, frontline nilotinib showed a favorable safety profile after 5 years of follow-up, but the 10-year follow-up showed a 25% cumulative incidence of cardiovascular events.¹⁵

Despite the significant improvement in outcomes with the approved third-generation TKIs, resistance still occurs. Patients with resistance to asciminib and/or ponatinib should be referred for clinical trials with newer-generation TKIs and should be considered for allogeneic stem cell transplantation.

Finally, TFR is an important goal of therapy in patients with CML. Multiple combination strategies have been evaluated but failed to improve the rates of TFR. It is preferable that patients attempting TFR achieve MR^4.5for 5 years or more before stopping TKI therapy.

BACK | NEXT

Clinical Education Alliance Terms and Conditions

These Terms of Use ("Terms") apply to your use of the websites, mobile applications and other resources provided by Clinical Education Alliance LLC (“CEA”) and its affiliates (referred to collectively as "CEA," "us," "we" and "our") that are intended for use by healthcare professionals, which we refer to as the "CEA Network," including the personalized information and services that meet the needs and interests of users of the CEA Network such as medical news, reference content, clinical tools, applications, sponsored programs, advertising, email communications, continuing medical education, market research opportunities and discussion forums (collectively, the "Services"). You will always be able to view the most current version of these Terms by clicking on the Terms of Use link at the bottom of any page of a CEA Network property. Note that these Terms do not apply to our properties and services that display a link to different terms of use. In the event that we expand the CEA Network through our acquisition of another company and/or its properties, that company may operate its properties subject to its own terms of use accessible via a link on such properties until we integrate its practices with ours, at which point a link to these Terms will be displayed on its properties. By using the Services, you agree to these Terms, whether or not you are a registered member of the CEA Network. These Terms govern your use of the Services and create a binding legal agreement that we may enforce against you in the event of a violation. If you do not agree to all of these Terms of Use, do not use the Services!

We reserve the right to change these terms from time to time. The most current version may be viewed by clicking on the “Terms of Use” link at the bottom of designated pages on the Clinical Education Alliance Sites. Use of the Clinical Education Alliance Sites after the effective date constitutes acceptance of the amended Terms of Use. When you leave a CEA Web site and go to another Web site, different terms apply and CEA has no responsibility or liability for any content on those sites.

Clinical Education Alliance Content

The Clinical Education Alliance Sites incorporate information, including modules, capsules, journal articles, medical news, references, interactive case studies, other continuing education material, downloadable software applications, advertising, and other healthcare information, which is intended for adults who are licensed healthcare professionals. This information is not intended to serve as a substitute for the healthcare professional’s clinical judgment. If you are a consumer who chooses to read this professional-level information on Clinical Education Alliance Sites, you should not use or rely on that information as professional medical advice or use it to replace any relationship with your physician or other qualified healthcare professional or any information they may have provided to you. For medical issues or concerns, including decisions about medications and other treatments, consumers should always consult their physician or, in serious cases, seek immediate assistance from emergency personnel.

The Content on the Clinical Education Alliance Sites is developed or selected in accordance with our published Editorial Policies. However, users access and use this material at their own risk. It is the reader’s job to evaluate the accuracy of any information and results from interactive programs found on the Clinical Education Alliance Site. If you are a healthcare professional, you should rely on your professional judgment in evaluating any and all information and confirm the information contained on the Clinical Education Alliance Sites with other sources and reliable third parties before basing any treatment or advice on it. If you are a consumer, you should evaluate the information together with your physician or another qualified healthcare professional.

DISCLAIMERS AND LIMITATIONS OF LIABILITY

THE CONTENT, APPLICATIONS, SOFTWARE, AND ALL OTHER MATERIAL ON THE CLINICAL EDUCATION ALLIANCE SITES ARE PROVIDED “AS IS” AND WITHOUT WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, OR NONINFRINGEMENT. ALL WARRANTIES, EXPRESS OR IMPLIED, ARE HEREBY DISCLAIMED. CLINICAL EDUCATION ALLIANCE SHALL NOT BE LIABLE FOR ANY SPECIAL, INCIDENTAL, OR CONSEQUENTIAL DAMAGES, INCLUDING, WITHOUT LIMITATION, PHYSICAL HARM OR INJURIES, LOST REVENUES, OR LOST PROFITS, RESULTING FROM THE USE OR MISUSE OF THE CLINICAL EDUCATION ALLIANCE SITES, OR ANY INFORMATION, APPLICATIONS, MATERIALS, OR SOFTWARE THEREON, EVEN IF CLINICAL EDUCATION ALLIANCE HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES, OR FOR ANY CLAIM BY ANOTHER PARTY. CLINICAL EDUCATION ALLIANCE DOES NOT WARRANT THAT THIS SITE OR ANY APPLICATIONS OR SOFTWARE WILL BE FREE OF BUGS, INACCURACIES, OR ERRORS, NOR DOES CLINICAL EDUCATION ALLIANCE WARRANT THAT ANY SITE, SOFTWARE, OR APPLICATION IS FREE OF VIRUSES OR OTHER HARMFUL ELEMENTS.

A user’s use of the Clinical Education Alliance Sites, and any reliance on any materials, information, software, or applications, is at the user’s own risk. You agree that you hereby release Clinical Education Alliance and its affiliates, owners, respective directors, officers, employees, advertisers, authors, and contributors from any and all liability or obligations arising from the use of the Clinical Education Alliance Sites. A user’s sole remedy for any problem or concern is to exit the Web site or application. You agree that you will indemnify and hold Clinical Education Alliance harmless for any loss, damages, or liability suffered by Clinical Education Alliance as a result of your use of any Clinical Education Alliance Site or material, application, information, or software thereon or your submission of any material to Clinical Education Alliance. Clinical Education Alliance reserves the right to restrict or limit access to this Web site.

CEA Programs, Tools, and Databases

The Clinical Education Alliance Sites include interactive programs, clinical tools, and databases intended for the use of healthcare professionals. These materials are not intended as professional advice or recommendations of particular products. Physicians and other healthcare professionals who use our interactive programs, tools, or databases should exercise their own clinical judgment as to the results. Consumers who use the tools or databases do so at their own risk.

Individuals with any type of medical condition are specifically cautioned to seek professional medical advice before beginning any sort of health treatment. For medical concerns or issues, including decisions about medications and other treatments, users should always consult their physician or other qualified healthcare professional.

Ownership of Clinical Education Alliance Sites—Copyright and Trademarks

The entire contents and design of the Clinical Education Alliance Sites, including the software applications, tools, and databases, are protected under US and international copyright laws. These materials are owned by CEA or its affiliates or are used with permission of their owners or as otherwise authorized by law. All rights are reserved, worldwide. You may look at the Clinical Education Alliance Sites, download individual articles or applications to your personal computer or handheld device, and print a reasonable number of pages for your own personal reference. You must not remove any copyright notices from our materials. We reserve all our other rights. This means you may not sell, rewrite, or modify any content or other material found on any Clinical Education Alliance Site, redistribute it, put it on your own Web site, or use it for any commercial purpose without our prior written authorization.

The names of the CEA products and services are protected by trademark laws in the United States. Any use of our trademarks or service marks requires prior written approval from CEA.

You may link to a CEA Web site if your Web site offers products, services, or information of interest to the professional healthcare community. You are not allowed to link to the Clinical Education Alliance Sites if you post illegal, obscene, or offensive content or if the link is likely to have a negative impact on CEA’s reputation. Any other use, such as framing any part of a CEA Web site or incorporating any CEA content into another Web site, product, or application, requires advance written permission from Clinical Education Alliance. Clinical Education Alliance assumes no responsibility for any Web sites or materials that are linked to Clinical Education Alliance Sites or materials.

Software Products and Applications

Clinical Education Alliance makes some software and accompanying documentation available for downloading from our Web sites and/or from iTunes. These materials are protected by copyrights under US and international law and are owned by Clinical Education Alliance or companies that have licensed the software to us. We do not transfer any ownership rights in software or documentation to you when you download it from our Web site and/or directly from iTunes. You may use the software and accompanying documentation for their intended purpose. You are not authorized to further copy or distribute the software and accompanying documentation, nor may you attempt to recreate or reverse engineer our software or applications. In addition, some software available for downloading from our Web sites and/or from iTunes is subject to US export controls. By downloading or using such software, you are representing to us that your download of such software complies with these controls.

US Government End Users

If you are affiliated with the US government, please note that the software and documentation available on our Web sites and/or directly from iTunes are “commercial items,” as that term is defined in 48 C.F.R. 2.101 (October 1995), consisting of “commercial computer software” and “commercial computer software documentation,” as such terms are used in 48 C.F.R. 12.212 (September 1995). Consistent with 48 C.F.R. 12.212 and 48 C.F.R. 227.7202-1 through 227.7202-4 (June 1995), all US government end users acquire the software and documentation with only those rights set forth herein.

Social Media, Message Boards, and Forums

Clinical Education Alliance offers users the opportunity to engage in social media interactions with both experts and other users of the sites. As with other online social media, users must exercise sound judgment in both the information that they post and in how they assess the postings of other users. As such, users are expected to adhere to the social media recommendations made by the American Medical Association when utilizing the social media capabilities of CEA sites. In particular, users must be cognizant of standards of patient privacy and confidentiality that must be maintained in all environments and must not post identifiable patient information on CEA sites. In social media interactions, users must maintain appropriate boundaries of the patient–physician/care provider relationship in accordance with professional ethical guidelines just as they would in any other context. Users acknowledge that privacy settings are not absolute and that once on the Internet, content posted by them may be copied by third parties and republished out of the control of Clinical Education Alliance. Thus, users should routinely monitor their own Internet presence to ensure that the personal information and content that they post and, to the extent possible, that is posted about them by others is accurate and appropriate.

Users are expected to refrain from submitting comments or messages that are defamatory, hateful, or obscene or that harass others. Users may not impersonate any other person or violate any other person’s or entity’s legal rights or submit falsified credentials or experiences. Users agree that they will not submit any materials that violate or infringe any copyrights, trademarks, patents, trade secret, or other intellectual property rights of any third party. Clinical Education Alliance retains all copyrights in the content posted by users to its sites. Clinical Education Alliance may adopt additional rules to govern use of social media, message boards or forums, to which users will be subject.

Copyright and Other Legal Violations

If you believe that any material on this Web site infringes your copyright, please notify us as follows, under the Digital Millennium Copyright Act (“DMCA”). To notify us, the DMCA requires that you: 1. Send an email notice to Clinical Education Alliance at customersupport@clinicaloptions.com. 2. Include the following information in your email: a. Identify the copyrighted work(s) you claim is infringed; b. Identify the material you claim is infringing the copyright(s) and give enough information for Clinical Education Alliance to locate that material; c. Include a physical or electronic signature of the copyright owner or a person authorized to act on the copyright owner’s behalf (the “Claimant”); d. Include the Claimant’s name, address, and telephone number(s); e. Include a statement that the Claimant has a good faith belief that use of the disputed material is not authorized by the copyright owner or his agent; and f. Include a statement, under penalty of perjury, that the information in the notification of copyright infringement is accurate and that the Claimant is the copyright owner or is authorized to act on behalf of the copyright owner.

If you believe any content or material on the Clinical Education Alliance Sites violates any laws, please notify customersupport@clinicaloptions.com. Please include details about your concerns and an email address for contacting you.

Governing Law

Clinical Education Alliance controls the Clinical Education Alliance Sites from its offices in the state of Virginia in the United States of America. The Clinical Education Alliance Sites can be accessed from any of the United States and from other countries worldwide. Since the laws of each state or country may differ, both you and Clinical Education Alliance agree that the laws of Virginia, without regard to conflicts of laws principles, will apply to all matters relating to use of the Clinical Education Alliance Sites and materials, including software and applications.

Clinical Education Alliance makes no representation that materials on these sites are appropriate or available for use in countries aside from the United States. Accessing the Clinical Education Alliance Sites from territories where their contents are illegal is prohibited. Those who choose to access these sites from other locations do so at their own risk and are responsible for compliance with any and all applicable local laws or regulations.

Acceptance Procedure

By downloading or accessing materials on the Clinical Education Alliance Sites and/or directly from iTunes or registering with us, you agree to all the terms and conditions in this agreement, including the Terms of Use and Privacy Policy. If you disagree with any of these Terms of Use or Privacy Policy, please refrain from using the Clinical Education Alliance Sites or materials.

Privacy Policy

Because we provide education for healthcare professionals, we pay special attention to privacy issues. The purpose of our Privacy Policy is to identify the information we may collect about you, describe the uses we may make of your information and the security measures we take to protect it, and discuss your options for controlling your information. You can review our Privacy Policy by clicking on the “Privacy Policy” link at the bottom of designated pages on the Clinical Education Alliance Sites.

Disputes

If you fail to comply with these terms, we have the right to suspend or eliminate your account and remove any information you have placed on our site, including your registration information. We may also take any legal action we think is appropriate. If there is any dispute between us concerning this agreement or your use of any Clinical Education Alliance Site or materials or applications, we both agree to submit the dispute to nonbinding mediation, followed by binding arbitration. Both the mediation and the arbitration will be governed under the rules of the American Arbitration Association, and the venue for the arbitration will be Virginia.

Questions or Concerns About Our Terms of Use

For questions or concerns about these Terms of Use, please send an email to customersupport@clinicaloptions.com

These terms of use were last updated in July 2021.