Ambient music plays. 

Disclaimers and Disclosures: Dr Seiter received compensation from Novartis Pharmaceuticals Corporation for her participation in this video.

 Please continue watching for the Important Safety Information for SCEMBLIX.

 Please see full Prescribing Information for SCEMBLIX at www.scemblix-hcp.com.

 Ambient music fades out.

 Dr Seiter: Hello. I’m Dr Seiter. I’m a hematologist and medical oncologist in New York.

 Dr Seiter: Over the past 60 years, we’ve witnessed transformative progress in the management of Philadelphia chromosome-positive CML in chronic phase, turning it from a usually fatal leukemia to a chronic disease with a life expectancy now approaching that of the general population. This revolutionary progress was largely due to advancements in treatment, starting with the approval of the first BCR::ABL1 tyrosine kinase inhibitors, or TKIs. 

Dr Seiter: This progress also introduced treatment goals, including molecular milestones such as major molecular response, or MMR, early molecular response, and deep molecular response or MR4. 

Dr Seiter: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recognize MMR at year 1 as an important milestone for patients with CML. NCCN Guidelines® response milestones after 1st-line TKI therapy. Based on the body of evidence across TKI therapies in CML, achieving major molecular response (MMR) in the first year has been associated with a very low probability of subsequent loss of response and a high likelihood of achieving a subsequent deep molecular response (DMR).

 Dr Seiter: However, even today, many newly diagnosed patients are unable to achieve MMR within the first year of treatment. For example, in newly diagnosed patients, registration studies reveal that up to 73% of those treated with a first-generation TKI and up to 54% treated with a second-generation TKI did not reach MMR by 12 months. 

Dr Seiter: In addition to issues with efficacy, data show that intolerance affects many patients in the newly diagnosed setting, and that in registration studies, up to 14% of patients discontinued treatment with their first TKI due to adverse reactions within the first year of treatment. 

Dr Seiter: This highlights a dual challenge: The difficulty in achieving efficacy milestones and the safety profile, including the risk of treatment discontinuation due to intolerance.

Therefore, an unmet need remains for additional treatments to help patients achieve key treatment milestones. Let’s now discuss the ASC4FIRST study.

Dr Seiter: ASC4FIRST was the only trial that evaluated all current standard-of-care TKI options for adults with newly diagnosed Philadelphia chromosome-positive CML in chronic phase. ASC4FIRST evaluated the efficacy, safety, and tolerability profile of SCEMBLIX versus imatinib, a commonly used TKI, and second-generation options nilotinib, dasatinib, or bosutinib.

NARRATOR: 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. Ph+ CML in CP with the T315I mutation.

Dr Seiter: Please continue watching at the end of this video for the Important Safety Information for SCEMBLIX.

Dr Seiter: Based in part on the results of this study, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), recommend asciminib as a NCCN Category 1, Preferred treatment option for patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase with any risk score. This recommendation marks an addition to the treatment landscape, offering another option for managing adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase. For additional information, visit scemblix-hcp.com.

Ambient music plays.

Dr Seiter: Please stay tuned for Important Safety Information.

Ambient music fades out.

NARRATOR: Important Safety Information for SCEMBLIX.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

Dr Seiter: Please see full Prescribing Information for SCEMBLIX at scemblix-hcp.com.

​Ambient music plays.

Disclaimers and disclosures: Dr Seiter received compensation from Novartis Pharmaceuticals Corporation for her participation in this video.

Please continue watching for the Important Safety Information for SCEMBLIX

Please see full Prescribing Information for SCEMBLIX at scemblix-hcp.com.

Ambient music fades out.

Dr Seiter: Hello. I’m Dr Seiter. I’m a hematologist and medical oncologist in New York.

Dr Seiter: The ASC4FIRST trial had a ground-breaking study design, which was reflective of clinical practices in the field of chronic myeloid leukemia, or CML. It was also the first study to evaluate all current standard-of-care tyrosine kinase inhibitor, or TKI, options for adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase.

NARRATOR: 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. Ph+ CML in CP with the T315I mutation.

Dr Seiter: Please continue watching at the end of this video for the Important Safety Information for SCEMBLIX.

Dr Seiter: Let’s delve a bit deeper into the ASC4FIRST study design. ASC4FIRST was a phase 3, multicenter, randomized, active-controlled, open-label study of 405 adults with newly diagnosed Philadelphia chromosome-positive CML in chronic phase that assessed the efficacy, safety, and tolerability profile of SCEMBLIX compared with imatinib, and 3 second-generation TKIs – nilotinib, dasatinib, or bosutinib.

Dr Seiter: Adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase were eligible to participate if they had not previously been treated with a TKI. A key feature that made ASC4FIRST unique was that, before randomization, physicians could select the appropriate TKI each patient would receive if assigned to the comparator arm. The investigator-selected TKIs, or IS-TKIs, were nilotinib, dasatinib, bosutinib, or imatinib. Patients were then randomized 1:1 to receive either SCEMBLIX or their preselected comparator TKI, with the randomization stratified by the preselected TKI and European Treatment and Outcome Study Long-Term Survival risk score. Both arms were divided into imatinib and second-generation TKI strata, with those in the SCEMBLIX arm receiving SCEMBLIX and those in the comparator arm receiving their predetermined TKI. 201 patients received SCEMBLIX at 80 mg qd, and 204 patients received IS-TKIs until unacceptable toxicity or treatment failure occurred.

Dr Seiter: Let’s take a closer look at the demographics of these patients. Most of the patients in the study were male. The median age of all patients was 51 years, with almost a quarter of the patients being 65 years or older. The majority of patients enrolled were either White or Asian, with a small percentage identifying as Black or African American.

Dr Seiter: The ASC4FIRST trial focused on 2 primary end points: MMR rates at week 48 for SCEMBLIX compared with all IS-TKIs and for SCEMBLIX versus IS-TKIs within the imatinib stratum. Additionally, key secondary end points included MMR rates at week 96, comparing SCEMBLIX with all IS-TKIs and SCEMBLIX with imatinib. Select other secondary end points explored were the MMR rates at week 48 and week 96 for SCEMBLIX versus IS TKIs within the 2G TKI stratum, the time to MMR, MR4 rates by scheduled time points, and MR2 rates by scheduled time points for SCEMBLIX versus IS-TKIs, along with a review of the safety and tolerability profile. A post hoc analysis was also conducted to evaluate the early molecular response for SCEMBLIX compared to IS-TKIs. Together, the data collected for these end points provided a comprehensive picture of the efficacy, safety, and tolerability profile of SCEMBLIX compared with the standard-of-care TKI options in the study.

Dr Seiter: By allowing investigators to select the comparator TKI, the ASC4FIRST study design was certainly innovative. More importantly, it reflected clinical practices, as investigators were able to adjust doses per local Prescribing Information, taking into account individual patient needs, tolerability, and response to treatment. For additional information about ASC4FIRST, visit scemblix-hcp.com.

Ambient music plays.

Dr Seiter: Please stay tuned for Important Safety Information.

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NARRATOR: Important Safety Information for SCEMBLIX.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

Dr Seiter: Please see full Prescribing Information for SCEMBLIX at scemblix-hcp.com.

​Ambient music plays.

Disclaimers and disclosures: Dr Seiter received compensation from Novartis Pharmaceuticals Corporation for her participation in this video.

Please continue watching for the Important Safety Information for SCEMBLIX

Please see full Prescribing Information for SCEMBLIX at scemblix-hcp.com.

Ambient music fades out.

Dr Seiter: Hi, My name is Dr Seiter. I’m a hematologist and medical oncologist in New York. As you might know, managing newly diagnosed Philadelphia chromosome-positive CML in chronic phase can be challenging. Patients rely on tyrosine kinase inhibitors, or TKIs, to reach their molecular response goals, but the journey can sometimes be difficult due to resistance or adverse reactions.

Dr Seiter: That’s where SCEMBLIX steps in, providing an additional treatment option for adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase.

NARRATOR: 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. Ph+ CML in CP with the T315I mutation.

Dr Seiter: Please continue watching at the end of this video for the Important Safety Information for SCEMBLIX.

Dr Seiter: SCEMBLIX was studied in the newly diagnosed setting in ASC4FIRST, which had a ground-breaking study design evaluating the efficacy, safety, and tolerability profile of SCEMBLIX versus investigator-selected TKIs, or IS-TKIs, imatinib, nilotinib, dasatinib, and bosutinib. ASC4FIRST was a multicenter, randomized, active-controlled, open-label study of 405 adults with newly diagnosed Philadelphia chromosome-positive CML in chronic phase. Investigators, in consultation with patients, preselected the appropriate TKI and evaluated ELTS risk scores. Patients were then stratified by preselected TKI and ELTS score, then randomized (1:1) to receive either SCEMBLIX or an investigator selected TKI. 201 patients received SCEMBLIX at 80 mg qd, and 204 patients received IS-TKIs until unacceptable toxicity or treatment failure occurred.

Dr Seiter: Let’s take a closer look at the demographics of these patients. Most of the patients in the study were male. The median age of all patients was 51 years, with almost a quarter of the patients being 65 years or older. The majority of patients enrolled were either White or Asian, with a small percentage identifying as Black or African American.

Dr Seiter: The 2 primary end points were MMR rate at week 48 for SCEMBLIX vs all IS-TKIs and MMR rate at week 48 for SCEMBLIX vs imatinib. Key secondary end points were MMR rate at week 96 for SCEMBLIX vs all IS-TKIs and MMR rate at week 96 for SCEMBLIX vs imatinib. There were also select other secondary end points.

Dr Seiter: Response rates with SCEMBLIX were superior to those with IS-TKIs. At week 48, 68% of patients achieved MMR with SCEMBLIX compared to 49% with all IS-TKIs. Within the imatinib stratum, 69% of patients attained MMR with SCEMBLIX versus 40% with imatinib. The median duration of treatment was 70 weeks (range, 1-108 weeks) for patients receiving SCEMBLIX and 64 weeks (range, 1-103 weeks) for patients receiving IS-TKIs. We see that at 96 weeks, MMR rates were 74% of patients with SCEMBLIX versus 52% with all IS-TKIs. Within the imatinib stratum, MMR rates were 76% of patients with SCEMBLIX versus 47% with imatinib. The median duration of treatment was 27 months (range, 0.2-36 months) for patients receiving SCEMBLIX and 25 months (range, 0.3-35 months) for patients receiving IS-TKIs.

Dr Seiter: Furthermore, at week 96, within the 2G TKIs stratum, response rates with SCEMBLIX were numerically higher than those with second-generation TKIs, with 72% for SCEMBLIX versus 57% for second-generation TKIs.

Dr Seiter: SCEMBLIX also worked fast, with a median time to MMR of 24 weeks compared to 36 weeks for all IS-TKIs and 49 weeks for imatinib.

Dr Seiter: Within the 2G TKIs stratum, median time to MMR was 24 weeks for SCEMBLIX, and for the second-generation TKIs was 36 weeks.

Dr Seiter: By week 48, MR4 rates were 41% of patients receiving SCEMBLIX compared to 22% of those receiving all IS-TKIs, and in the imatinib stratum MR4 rates were 46% of patients with SCEMBLIX versus 16% with imatinib. By week 96, MR4 rates were 53% of patients on SCEMBLIX compared to 34% of those on all IS-TKIs. And within the imatinib stratum, these numbers were 56% for SCEMBLIX versus 28% for imatinib.

Dr Seiter: If we look at the second-generation TKI stratum, we see that MR4 rates were 36% for patients on SCEMBLIX compared to 28% for those on second-generation TKIs by 48 weeks. By 96 weeks, MR4 rates were 49% for SCEMBLIX and 40% for second-generation TKIs.

Dr Seiter: Let's take a closer look at discontinuation rates. SCEMBLIX discontinuation rates due to ARs were more than 2 times lower than those for all IS-TKIs. At week 96, 5.0% of patients with SCEMBLIX (n=200) permanently discontinued treatment due to ARs, compared to 12.9% with all IS-TKIs, 13.1% with imatinib, and 12.7% with second generation TKIs.

Dr Seiter: Dose reductions due to adverse reactions occurred in 6% of SCEMBLIX patients at week 48. Adverse reactions caused dosage interruptions in 30% of SCEMBLIX patients at 48 weeks. Moving to the 96-week mark, 6% of patients on SCEMBLIX needed dose reductions and 33% of patients needed dose interruptions due to adverse reactions. Across the board, adverse reactions that required dose reductions in more than 1% of patients or dosage interruptions in more than 5% of patients included thrombocytopenia and neutropenia.

Dr Seiter: This brings us to the safety profile. At week 48, the most common adverse reactions that occurred with SCEMBLIX in at least 10% of patients were musculoskeletal pain, rash, fatigue, diarrhea, abdominal pain, upper respiratory tract infection, dyslipidemia, and headache.

Dr Seiter: Serious ARs occurred in 11% of patients who received SCEMBLIX. Serious ARs seen in ≥1% included pancreatitis and musculoskeletal pain.

Dr Seiter: Lab abnormalities were also observed. Select parameters that worsened from baseline in at least 20% of SCEMBLIX patients at week 48 included decreased lymphocyte count, leukocyte count, platelet count, neutrophil count, hemoglobin and corrected calcium levels, and increased lipase, cholesterol, uric acid, alanine aminotransferase, alkaline phosphatase, and triglycerides.

Dr Seiter: The safety profile of SCEMBLIX continued to be monitored through week 96. Shown here are the adverse reactions that occurred in at least 10% of patients, which included musculoskeletal pain, arthralgia, rash, fatigue, diarrhea, abdominal pain, constipation, upper respiratory tract infection, dyslipidemia, headache, and hypertension.

NARRATOR: Serious adverse reactions occurred in 15% of patients who received SCEMBLIX. Serious adverse reactions in ≥1% included pancreatitis (1%), musculoskeletal pain (1%), and peripheral neuropathy (1%).

Dr Seiter: Select parameters that worsened from baseline in at least 20% of SCEMBLIX patients at week 96 included decreased lymphocyte count, leukocyte count, platelet count, neutrophil count, hemoglobin and corrected calcium levels, and increased lipase, cholesterol, uric acid, alanine aminotransferase, alkaline phosphatase, and triglycerides.

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Dr Seiter: For additional information, including the full Prescribing Information, visit scemblix-hcp.com.

Dr Seiter: Please stay tuned for Important Safety Information.

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NARRATOR: Important Safety Information for SCEMBLIX. NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

Dr Seiter: Please see full Prescribing Information for SCEMBLIX at scemblix-hcp.com.

​Ambient music plays.

Disclaimers and disclosures: Dr Seiter received compensation from Novartis Pharmaceuticals Corporation for her participation in this video.

Please continue watching for the Important Safety Information for SCEMBLIX

Please see full Prescribing Information for SCEMBLIX at scemblix-hcp.com.

Ambient music fades out.

Dr Seiter: Hello. I’m Dr Seiter. I’m a hematologist and medical oncologist in New York. As health care professionals, we understand the challenges involved in choosing a first-line treatment for patients with Philadelphia chromosome-positive chronic myeloid leukemia, or CML, in chronic phase. That’s why I’m excited to share with you some important safety and tolerability profile findings from the ASC4FIRST trial, which had a ground-breaking study design and compared the efficacy, safety, and tolerability profile of SCEMBLIX with commonly used imatinib, nilotinib, dasatinib, and bosutinib, in adults with newly diagnosed Philadelphia chromosome-positive CML in chronic phase.

NARRATOR: 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. Ph+ CML in CP with the T315I mutation.

Dr Seiter: Please continue watching at the end of this video for the Important Safety Information for SCEMBLIX.

Dr Seiter: ASC4FIRST was a multicenter, randomized, active-controlled, open-label study of 405 adults with newly diagnosed Philadelphia chromosome-positive CML in chronic phase. Investigators, in consultation with patients, preselected the appropriate TKI and evaluated ELTS risk scores. Patients were then stratified by preselected TKI and ELTS score, then randomized (1:1) to receive either SCEMBLIX or an investigator-selected TKI. 201 patients received SCEMBLIX at 80 mg qd, and 204 patients received IS-TKIs until unacceptable toxicity or treatment failure occurred.

Dr Seiter: Let’s take a closer look at the demographics of these patients. Most of the patients in the study were male. The median age of all patients was 51 years, with almost a quarter of the patients being 65 years or older. The majority of patients enrolled were either White or Asian, with a small percentage identifying as Black or African American.

Dr Seiter: Let’s turn our attention to discontinuation data. At week 96, we see that SCEMBLIX discontinuation rates due to adverse reactions were more than 2 times lower than those for all IS-TKIs. At 96 weeks, we see that 5% of patients who received SCEMBLIX permanently discontinued treatment due to adverse reactions versus 12.9% receiving all IS-TKIs, 13.1% on imatinib, and 12.7% receiving second-generation TKIs.

Dr Seiter: Some patients required either dose reductions or interruptions during the trial. At week 48, 6% of SCEMBLIX patients experienced dose reductions and 30% experienced dosage interruptions due to adverse reactions. At 96 weeks, adverse reactions led to dose reductions in 6% of patients and dosage interruptions in 33% of patients on SCEMBLIX. Thrombocytopenia and neutropenia were the most common adverse reactions that caused dose reductions or interruptions at either time point.

Dr Seiter: Shifting our focus slightly, let’s examine the safety results for SCEMBLIX and all IS-TKIs. In the Week 48 analysis, adverse reactions that occurred in at least 10% of patients who received SCEMBLIX were musculoskeletal pain, rash, fatigue, diarrhea, abdominal pain, upper respiratory tract infection, dyslipidemia, and headache.

Dr Seiter: It’s important to note that serious adverse reactions occurred in 11% of patients who received SCEMBLIX. And those seen in 1% or more included pancreatitis and musculoskeletal pain.

Dr Seiter: ASC4FIRST also assessed lab abnormalities at 48 weeks. Select lab abnormalities that worsened from baseline in at least 20% of patients on SCEMBLIX included hematologic and biochemical changes such as decreased lymphocyte count, leukocyte count, platelet count, neutrophil count, hemoglobin, and corrected calcium levels, and increased lipase, cholesterol, uric acid, alanine aminotransferase, alkaline phosphatase, and triglycerides.

Dr Seiter: The safety profile continued to be evaluated out to week 96; adverse reactions that occurred in at least 10% of patients who received SCEMBLIX were musculoskeletal pain, arthralgia, rash, fatigue, diarrhea, abdominal pain, constipation, upper respiratory tract infection, dyslipidemia, headache, and hypertension.

NARRATOR: Serious adverse reactions occurred in 15% of patients who received SCEMBLIX. Serious adverse reactions seen in ≥1% of patients included pancreatitis (1%), musculoskeletal pain (1%), and peripheral neuropathy (1%).

Dr Seiter: Week 96 lab abnormalities occurring in at least 20% of patients on SCEMBLIX are shown here. The most common select laboratory abnormalities that worsened from baseline in at least 20% of patients who received SCEMBLIX were decreased lymphocyte count, leukocyte count, platelet count, neutrophil count, hemoglobin, and corrected calcium levels, and increased lipase, cholesterol, uric acid, alanine aminotransferase, alkaline phosphatase, and triglycerides.

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Dr Seiter: To learn more about SCEMBLIX for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive CML in chronic phase, visit scemblix hcp.com.

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Dr Seiter: Please stay tuned for Important Safety Information.

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NARRATOR: Important Safety Information for SCEMBLIX.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

NARRATOR: 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.

Dr Seiter: Please see full Prescribing Information for SCEMBLIX at scemblix-hcp.com.
 

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