About this episode
"All of these TKIs [tyrosine kinase inhibitors] inhibit BCR-ABL1 in some way, shape, or form. When BCR-ABL1 is mutated, it has uncontrolled tyrosine kinase activity, leading to rapid cell proliferation. When we then inhibit that BCR-ABL1 that's been mutated, we disrupt this abnormal signaling pathway that drives CML [chronic myeloid leukemia] cell proliferation and survival, ultimately leading to decreased cancer cell growth, increased apoptosis or cell death, and potentially inducing a disease remission," Samantha Maples, PharmD, BCOP, clinical pharmacy specialist supervisor for hematology and cellular therapy at Allegheny Health Network in Pittsburgh, PA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the BCR-ABL1 inhibitor drug class. Music Credit: " Fireflies and Stardust " by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by September 5, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learner will report an increase in knowledge related to the use of BCR-ABL1 inhibitors in the treatment of CML. Episode Notes Complete this evaluation for free NCPD . ONS Podcast ™ episodes: Pharmacology 101 series Episode 322: Nursing Strategies to Reduce Readmission Rates for Patients With Cancer Episode 215: Navigate Updates in Oral Adherence to Cancer Therapies ONS Voice articles: Adherence to Oral Anticancer Medication Combination Therapy Shows Promise for Chronic Myeloid Leukemia The Case of the Medication Modification The Case of the Safety Session ONS course: Safe Handling Basics Clinical Journal of Oncology Nursing articles: Targeted Drug Therapies: Beyond Blood Counts and Chemistries Oncology Nursing Forum articles: Adherence and Coping Strategies in Outpatients With Chronic Myeloid Leukemia Receiving Oral Tyrosine Kinase Inhibitors Fear of Progression in Outpatients With Chronic Myeloid Leukemia on Oral Tyrosine Kinase Inhibitors Other ONS resources: Biomarker Database Financial Toxicity Huddle Card Tyrosine Kinase Inhibitors Huddle Card Oral Anticancer Medication Care Compass: Resources for Interprofessional Navigation Oral Anticancer Medication Learning Library National Comprehensive Cancer Network National Comprehensive Cancer Network patient resources To discuss the information in this episode with other oncology nurses, visit the ONS Communities . To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library . To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org . Highlights From This Episode "The IRIS study led to the approval of the BCR-ABL1 and TKI, imatinib, for CML in 2001 and completely changed the landscape of CML treatment. Then came the second-generation BCR-ABL1 TKIs: dasatinib in 2006, quickly followed by nilotinib in 2007. Thereafter came our second-generation, bosutinib, and our first approved third-generation TKI, ponatinib, both in 2012, which was a huge milestone as ponatinib overcomes resistance to the T315 I mutation, which no previously approved TKIs worked against." TS 2:16 "The newest approved TKI, asciminib, is an allosteric inhibitor that binds to a different pocket on the BCR-ABL kinase via allosteric binding to the ABL myristoyl pocket. It's what's called a STAMP inhibitor, where STAMP stands for 'specifically targeting the ABL myristoyl pocket.' And while all the TKIs target the BCR-ABL1 binding site, they can also inhibit different off-target kinases. And these differences in off-target inhibition are responsible for some of the different toxicities we see among the TKIs." TS 4:51 "As a class, common toxicities include nausea; vomiting; diarrhea; cardiac toxicities, including cardiac arrhythmias and congestive heart failure; metabolic abnormalities such as hypercholesterolemia and hypertriglyceridemia; nephrotoxicity; hepatic toxicity; hemorrhaging and bleeding; as well as cytopenia. Individually, some of these agents are more likely to cause certain side effects compared to others, and there are unique toxicities associated with certain TKIs." TS 8:10 "We've moved to using preemptive loperamide [in our clinic] for the first three days of starting treatment, because it's really hard to get patients to continue to take a medication if they have such severe diarrhea that they end up in the hospital or they're unable to leave their house. A lot of times, we will proactively give patients antiemetics and loperamide to help with the nausea, vomiting, and diarrhea. And then we can back off to an as-needed basis once they've been established on treatment. We can also use medications to help manage long-term complications that can require supportive care, such as statin therapy for high cholesterol, levothyroxine for hypothyroidism, anticoagulants for any venous thromboembolism, and antihypertensive medications for managing any new or worsening high blood pressure." TS 12:44 "We are continually seeing these agents expand their indications to different lines of therapy, as well as more TKIs being approved for acute lymphoblastic leukemia. For example, asciminib just got approved in the frontline setting within the last year, whereas previously it was only approved in relapsed refractory setting. Last year, imatinib was the first BCR-ABL1 TKI to come out with a commercially supplied suspension option as well, which is huge in the pediatric space and [for] our adult patients who are unable to swallow tablets for other clinical reasons." TS 21:22 "There is more information being published on the safe discontinuation of these medications with treatment-free remissions, and more information is coming out about who would be eligible and who can have the option to stop these treatments instead of having a lifelong chronic condition requiring continuous treatment. We're seeing more patients in clinical practice be able to stop BCR-ABL1 treatment, which has been a great development in CML." TS 25:29