Five Factors That Guide How I Treat Adults with Chronic Myeloid Leukemia in Chronic Phase

Content sponsored by Novartis Pharmaceuticals Corporation. Payment for Dr Strickland's participation has been made to his institution.

The treatment landscape for chronic myeloid leukemia (CML) has transformed dramatically over the past 2 and a half decades. With the emergence of tyrosine kinase inhibitors (TKIs), CML was transformed from a usually fatal leukemia to a chronic disease with a life expectancy approaching that of the general population.^1,2

With progress, however, comes the need to continually assess how we approach care. New data, evolving guidelines, and day-to-day patient experiences all influence how I approach care. As more options become available, the choices we make—particularly in the first-line setting—matter.

Here are the 5 key factors that guide how I treat adult patients with Philadelphia chromosome-positive CML in chronic phase (Ph+ CML-CP) in my practice:

1. First-Line Choice Isn’t Just a Starting Point—It’s the Foundation

There is a growing body of evidence suggesting that achieving major molecular response (MMR) is a critical treatment milestone.³ With the availability of second-generation, third-generation, and allosteric TKIs, we have agents that can help patients achieve molecular responses.²

With Ph+ CML-CP, the choice of first-line therapy can be an important step on the treatment journey.³ It's not just about initiating treatment—it’s about choosing a regimen that may offer an individual patient an opportunity to achieve MMR and a deep molecular response while considering the treatment’s safety/tolerability profile.

If we delay the use of our most effective tools, patients may miss the opportunity to achieve early molecular responses. Starting with a treatment option that offers the opportunity to achieve MMR and deep molecular response may give patients a chance to reach key milestones.⁴

2. Safety and Tolerability Profile Matters as Much as Efficacy

Tolerability can take on many faces. At the time of a new diagnosis, when patients hear the word “leukemia,” they’re usually motivated to get the disease under control.

But what patients are willing to tolerate at diagnosis is different from what they’ll accept 6, 9, or 12 months down the line. The “leaky faucet” of side effects that may have felt like manageable “drips” at first can become increasingly burdensome over time. Even when a patient's disease is well controlled, tolerability issues can be the difference between staying on treatment, discontinuing treatment, or not taking it as prescribed.

Patients who feel their side effects are manageable for them may be more likely to stay on therapy.⁵ In CML, where most people take treatment for the rest of their lives, the safety and tolerability profile of therapy is important.⁶

3. Guideline Recommendations and Clinical Data

Historically, many of us chose to stay with the familiar. But that approach is shifting, driven by updated guidelines and emerging data.

The latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) include asciminib (SCEMBLIX®) as an NCCN category 1, preferred first-line option for adults with newly diagnosed Ph+ CML-CP, across all risk categories (low-, intermediate-, or high-risk score).*

SCEMBLIX^® (asciminib) 40-mg tablets is indicated for the treatment of adult patients with newly diagnosed and previously treated Ph+ CML-CP. The newly diagnosed indication is approved under accelerated approval based on major molecular response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s). Please see Important Safety Information below.

Clinical trial data for asciminib—the first and only approved inhibitor that binds to the ABL myristoyl pocket⁷—provides clinicians with more to consider when evaluating whether this medication aligns with the treatment goals of their adult patients with newly diagnosed Ph+ CML-CP.

ASC4FIRST was a multicenter, randomized, active-controlled, open-label study of 405 adults with newly diagnosed Ph+ CML-CP. Investigators, in consultation with patients, preselected the appropriate TKI and evaluated patients' EUTOS long-term survival (ELTS) risk scores. Patients were then stratified by preselected TKI and ELTS score. Once stratified, they were randomized (1:1) to receive either asciminib or an Investigator-selected TKI (imatinib, nilotinib, bosutinib, or dasatinib). 201 patients received asciminib at 80 mg qd, and 204 patients received IS-TKIs until unacceptable toxicity or treatment failure occurred.^7,8

In the two primary end points of the ASC4FIRST trial, asciminib (n=201) showed superior MMR rates at week 48 compared with investigator-selected standard-of-care TKIs^† (n=204) (68% [95% CI, 61-74] vs 49% [42-56]; difference 19%; 95% CI^‡ 10-28); p<0.001^§ ).⁷ In the imatinib stratum, asciminib (n=101) showed superior MMR rates compared to IS-TKI (imatinib) (n=102) (69% [95% CI, 59-78] vs 40% [95% CI, 31-50]; difference 30%; 95% CI ^‡ 17-42; p<0.001^¶) at week 48.⁷ The most common AR (≥20%) at 48 weeks in patients who received asciminib was musculoskeletal pain.⁷

At 96 weeks, the MMR rate was 74% (95% CI, 68-80) in the asciminib group (n=201) and 52% (95% CI, 45-59) in the IS-TKI(all)^† group (n=204).⁹ In the imatinib stratum at 96 weeks, there was an MMR rate of 76% (95% CI, 67-84) in the asciminib group (n=101) and 47% (95% CI, 37-57) in the IS-TKI imatinib group (n=102).⁹ The most common ARs (≥ 20%) at 96 weeks in patients who received asciminib were musculoskeletal pain and rash.¹⁰

There are warnings and precautions associated with asciminib, including myelosuppression, pancreatic toxicity, hypertension, hypersensitivity, cardiovascular toxicity, and embryo-fetal toxicity.⁷ To learn more about asciminib, including additional Important Safety Information and full Prescribing Information, see below and visit SCEMBLIX-hcp.com.

These clinical findings support what I’ve been seeing in my practice in terms of asciminib MMR rates compared to commonly used TKIs^†.⁷

For me, these results—combined with my own experience of prescribing asciminib—represent a shift in how some patients are treated. The strength of the data and the inclusion of asciminib as a recommended treatment option in the latest NCCN Guidelines®* reinforce its potential.

4. Access Needn’t Be a Barrier to Care

When considering various therapies, concerns about access often come up. Will insurance cover it? Will patients face delays?

These are valid questions and, in my experience, they can often be resolved before they become barriers. Patient access programs can be instrumental in helping patients access their prescribed therapies.

These programs may help patients—whether insured, uninsured, underinsured, or navigating a complex approval process—access the therapy we believe is most appropriate for them.

In my practice, I’ve found the process of prescribing asciminib and starting patients on therapy to be straightforward. Our practice has found that aligning requests with the ASC4FIRST data and NCCN Guidelines®* has been effective in starting appropriate candidates for asciminib on therapy without delays or administrative hurdles.

5. Strong Patient-Provider Dialogue Is Key

Delivering a diagnosis like CML isn’t just a clinical moment—it’s a human one. As physicians, we’re armed with knowledge, and our instinct is often to dive into the data, the treatment plan, and the path forward. That’s our comfort zone. But when you’re telling a patient they have CML, you have to pause and give them space to process. In some cases, it means having them come back for a second conversation once they’ve had time to absorb the news.

That pause can be powerful. It creates space for reflection and shared decision-making, as well as an opportunity to align on what matters most to the patient. No 2 patients are alike and, when choosing a first-line treatment, I strongly believe our patients’ preferences, concerns, and goals should guide the conversation as much as our own expertise in the field.

It’s a foundation of trust that pays dividends. Open, ongoing dialogue is critical, and I actively seek out my patients’ feedback throughout their care journey. However, it’s not just about how their labs look, but what they’re thinking. What’s working and, just as critically, what’s not.

When patients are part of the decision-making process from the beginning, it strengthens the relationship. Most importantly, it ensures we’re not just treating the disease—we’re treating the person.

Grounding Treatment Decisions in Evidence and Experience

As our understanding of CML continues to evolve, so should our approach to treatment. I aim to make decisions that are grounded in clinical evidence, informed by patient experience, and responsive to the realities of long-term disease management.

There is no one-size-fits-all approach. But with the right tools and an open dialogue, we can better support each patient on their individual journey with CML.

To learn more about asciminib, visit SCEMBLIX-hcp.com and see below for Important Safety Information and full Prescribing Information.

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia Version 1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 14, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
^†Imatinib, nilotinib, dasatinib, and bosutinib
^‡Estimated using a common risk difference stratified by PRS-TKI and baseline ELTS risk groups^7
§Adjusted P-value using a Cochran-Mantel-Haenszel 1-sided test stratified by PRS-TKI and baseline ELTS risk groups^7
¶Adjusted P-value using a Cochran-Mantel-Haenszel 1-sided test stratified by baseline ELTS risk groups⁷

Indications
SCEMBLIX^® (asciminib) tablets is indicated for the treatment of adult patients with:

• Newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP)
  • This indication is approved under accelerated approval based on major molecular response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s)
• Previously treated Ph+ CML in CP

IMPORTANT SAFETY INFORMATION for SCEMBLIX
Myelosuppression

• Thrombocytopenia, neutropenia, and anemia, including grade 3/4 reactions, have occurred in patients receiving SCEMBLIX
• Perform complete blood counts every 2 weeks for the first 3 months of treatment and monthly thereafter or as clinically indicated. Monitor patients for signs and symptoms of myelosuppression
• Based on the severity of thrombocytopenia and/or neutropenia, reduce dose, temporarily withhold, or permanently discontinue SCEMBLIX as described in the prescribing information

Pancreatic Toxicity

• Pancreatitis (including grade 3 reactions) and elevation in serum lipase and amylase (including grade 3/4 elevations), have occurred in patients receiving SCEMBLIX
• Assess serum lipase and amylase levels monthly during treatment with SCEMBLIX, or as clinically indicated. Monitor patients for signs and symptoms of pancreatic toxicity. Perform more frequent monitoring in patients with a history of pancreatitis
• If lipase and amylase elevation are accompanied by abdominal symptoms, temporarily withhold SCEMBLIX and consider appropriate diagnostic tests to exclude pancreatitis
• Based on the severity of lipase and amylase elevation, reduce dose, temporarily withhold, or permanently discontinue SCEMBLIX as described in the prescribing information

Hypertension

• Hypertension, including grade 3/4 reactions, have occurred in patients receiving SCEMBLIX
• Monitor and manage hypertension using standard antihypertensive therapy during treatment with SCEMBLIX as clinically indicated
• For grade 3 or higher reactions, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX as described in the prescribing information depending on persistence of hypertension

Hypersensitivity

• Hypersensitivity, including grade 3/4 reactions, have occurred in patients receiving SCEMBLIX. Reactions included rash, edema, and bronchospasm
• Monitor patients for signs and symptoms and initiate appropriate treatment as clinically indicated
• For grade 3 or higher reactions, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX as described in the prescribing information depending on persistence of hypersensitivity

Cardiovascular Toxicity

• Cardiovascular toxicity (including ischemic cardiac and central nervous system conditions; and arterial thrombotic and embolic conditions) and cardiac failure have occurred in patients receiving SCEMBLIX. Some toxicities were grade 3/4 and 5 fatalities were reported
• Arrhythmia, including QTc prolongation, have occurred in patients receiving SCEMBLIX. Some of these arrhythmias were grade 3/4
• Monitor patients with a history of cardiovascular risk factors for cardiovascular signs and symptoms. Initiate appropriate treatment as clinically indicated
• For grade 3 or higher cardiovascular toxicity, temporarily withhold, reduce dose, or permanently discontinue SCEMBLIX as described in the prescribing information depending on persistence of cardiovascular toxicity

Embryo-Fetal Toxicity

• SCEMBLIX can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus if SCEMBLIX is used during pregnancy or if the patient becomes pregnant while taking SCEMBLIX
• Verify the pregnancy status of females of reproductive potential prior to starting treatment with SCEMBLIX. Advise females to use effective contraception during treatment and for at least 1 week after the last SCEMBLIX dose

ADVERSE REACTIONS

• Most common adverse reactions (≥20%) were musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, arthralgia, and diarrhea
• Most common select laboratory abnormalities (≥20%) were lymphocyte count decreased, leukocyte count decreased, platelet count decreased, neutrophil count decreased, calcium corrected decreased, lipase increased, cholesterol increased, uric acid increased, alanine aminotransferase increased, alkaline phosphatase increased, hemoglobin decreased, triglycerides increased, creatine kinase increased, amylase increased, and aspartate aminotransferase increased

DRUG INTERACTIONS

• Asciminib is an inhibitor of CYP3A4, CYP2C9, P-gp, and BCRP. Asciminib is a CYP3A4 substrate
• Closely monitor for adverse reactions during concomitant use of strong CYP3A4 inhibitors and SCEMBLIX at 200 mg twice daily
• Avoid concomitant use of itraconazole oral solution containing hydroxypropyl-β-cyclodextrin and SCEMBLIX at all recommended doses
• Closely monitor for adverse reactions during concomitant use of certain CYP3A4 substrates and SCEMBLIX at 80 mg total daily dose. Avoid use of SCEMBLIX at 200 mg twice daily
• Avoid concomitant use of CYP2C9 substrates and SCEMBLIX at all recommended doses. If coadministration with 80 mg total daily dose is unavoidable, reduce the CYP2C9 substrate dosage as recommended in its prescribing information. If coadministration with 200 mg twice daily is unavoidable, consider alternative therapy with a non-CYP2C9 substrate
• Closely monitor for adverse reactions during concomitant use of certain P-gp substrates and SCEMBLIX at all recommended doses
• Avoid concomitant use of rosuvastatin and SCEMBLIX at all recommended doses. Closely monitor for adverse reactions during concomitant use of other BCRP substrates and SCEMBLIX at all recommended doses

Please see full Prescribing Information.

References

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4. Quintás-Cardama A, Kantarjian H, Jones D, et al. Blood. 2009;113(25):6315–6321. https://doi.org/10.1182/blood-2008-07-166694
5. Geissler J, Sharf G, Bombaci F, et al. J Cancer Res Clin Oncol. 2017;143:1167–1176. https://doi.org/10.1007/s00432-017-2372-z
6. Daily life, support and chronic myeloid leukaemia (CML). (2025). Cancer Research UK. Accessed November 6, 2025. https://www.cancerresearchuk.org/about-cancer/chronic-myeloid-leukaemia-cml/living-with/daily-life
7. Scemblix. Prescribing information. Novartis Pharmaceuticals Corp.
8. Data on file. CABL001J12301 clinical study report (Week 48 analysis). Novartis Pharmaceuticals Corp; 2024.
9. Data on file. CABL001J12301 clinical study report (Week 96 analysis). Novartis Pharmaceuticals Corp; 2024.
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