Scemblix (asciminib) / Novartis - LARVOL DELTA

Imatinib in chronic myeloid leukemia: A comparative assessment of patients in pivotal clinical trials and real-world settings (ASH 2025) - " We included the imatinib arm of 5 pivotal CTs: the IRIS, which established the superiority of imatinib over interferon alfa plus cytarabine, and the DASISION, ENESTnd, BFORE, and ASC4FIRST trials, which supported the approvals of dasatinib, nilotinib, bosutinib, and asciminib, respectively. Patients in the RWD cohort exhibited higher clinical risk profiles, greater racial and ethnic diversity, and longer intervals between diagnosis and treatment initiation. These factors may contribute to the lower rates of achieving optimal treatment responses, including cytogenetic and molecular milestones. Despite these differences, long-term outcomes were comparable, aligning with current trends showing that survival in CML patients now approaches that of the general population."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Real-world analysis of asciminib as first-line therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A chart review Study in the United States (ASH 2025) - P3 | "These early real-world findings support the effectiveness and tolerability of asciminib as initial treatment for patients with newly diagnosed CML-CP in the US clinical practice setting. Additional chart review is currently underway, with analyses planned on a larger sample size and extended follow-up to evaluate molecular response."

Clinical • Real-world • Real-world evidence • Review • Chronic Myeloid Leukemia • Chronic Obstructive Pulmonary Disease • Hematological Malignancies • Hypertension • Immunology • Leukemia • Pulmonary Disease • Respiratory Diseases

Asciminib pediatric formulation shows a tolerable safety profile in pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP): Second interim analysis from the ASC4KIDS study (ASH 2025) - P1/2 | "Preliminary data suggest that asciminib, unlike other TKIs, may not have a negative impact on growth in most patients. In study part 3, a 2.6 mg/kg QD dose will be assessed."

Clinical • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Pediatrics • Respiratory Diseases

Asciminib as initial therapy with addition of lower dose tyrosine kinase inhibitors (TKIs) for patients with chronic myeloid leukemia who do not achieve optimal response or a deep molecular remission (ASH 2025) - P2 | "Patients who did not achieve MR4.5 after 24 months on asciminib, experienced treatment failure at any time or had a warning response at 12 months were offered the addition of lowTKI (imatinib 300 mg, dasatinib 50 mg or nilotinib 300 mg daily). Asciminib monotherapy demonstrated rapid early and deep molecular responses in patients with CP-CML, with a favorable safety profile. Further data will be presented for patients who added lowTKI."

Clinical • Chronic Myeloid Leukemia • CNS Disorders • Dermatology • Hypertension • Insomnia • Musculoskeletal Pain • Neutropenia • Pancreatitis • Sleep Disorder • Thrombocytopenia • ABL1

Chemotherapy free ponatinib + asciminib achieves optimal disease controlpreallohsct in advanced – CML (ASH 2025) - "Pt1: Male, CML diagnosed at age 21; prior TKIs: imatinib, dasatinib, bosutinib; progressed to CML-BC at age 26; no response to ponatinib in monotherapy after two months so asciminib was added for 1 months of combination therapy. The distinct yet complementary mechanisms of TKIs were well tolerated in pt 1 and 2; its use in patients older than 50 years could require caution moreover if precedently treated with nilotinib. These preliminary results warrant further confirmation in larger prospective trials."

Metastases • Chronic Myeloid Leukemia • Myocardial Infarction • ABL1

Real-world data comparison of asciminib 40 mg twice daily vs. 80 mg once daily in chronic myeloid leukemia patients (ASH 2025) - "Introduction: Asciminib (ASC) is a first-in-class Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor that binds to the ABL myristoyl pocket. In this real-world analysis, both ASC 40 mg BID and 80 mg QD demonstrated similar response rates and favorable AE profiles in CML-CP pts previously treated with ≥2 TKIs, with the limitation of a relatively small sample size. Overall efficacy was well maintained. The QD regimen was associated with fewer dose escalations and discontinuation rate, supporting its convenience and potentially advantageous dosing strategy in clinical practice."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Musculoskeletal Diseases • Musculoskeletal Pain • Pancreatitis • Thrombocytopenia • ABL1

Asciminib in chronic myeloid leukemia: Superior efficacy and favorable safety outcomes from a systematic review and meta-analysis (ASH 2025) - "Asciminib significantly improved MMR during follow-up compared to the control group and and demonstrates a favorable safety profile, with a reduced risk of grade ≥3 AEs compared with second-generation TKIs. Subgroup analyses will be performed based on asciminib dose and prior use of TKIs for the primary outcome."

Retrospective data • Review • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Respiratory Diseases • Thrombocytopenia • ABL1

Asciminib as monotherapy or adjunctive therapy for chronic myeloid leukaemia in blast phase (ASH 2025) - "Asciminib was used in conjunction with another ATP-binding TKI in 5 (71%) patients (ponatinib, N=4; dasatinib, N=1); three of whom also received additional treatment (venetoclax and hypomethylating agents, N=2; intensive chemotherapy, N=1). Asciminib-based regimen was well tolerated, with only grade 1-2 non-haematological toxicities in 3 patients (hepatotoxicity, N=1; rash, N=1; myalgia, N=1) and grade 2 or above cytopenia in 3 patients.Conclusions The retrospective nature and small cohort size of our study notwithstanding, our analysis of this real-life cohort of CML-BP patients showed promising activity and reassuring safety profile of asciminib-based regimens. Patients experiencing ponatinib failure could potentially be salvaged by asciminib-based treatment."

Monotherapy • Chronic Myeloid Leukemia • Hematological Malignancies • Musculoskeletal Pain • ABL1

Feasibility of the edmonton symptom assessment system (ESAS) score as patient-reported outcomes (PROs) assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy: A pilot Study (ASH 2025) - "TKIs most frequently used before discontinuation were dasatinib (n=8 out of 27 pts, 30%), bosutinib (n=3/8, 37%), imatinib (n=3/5, 60%), nilotinib (n=2/6, 33%), and asciminib (n=2/27, 7%). Additionally, ESAS may be valuable for longitudinal follow-up to assess symptom evolution after treatment changes. Prospective studies with larger cohorts are warranted to validate these observations and determine whether symptom-guided strategies can improve TKI adherence and clinical outcomes in CML."

Clinical • Patient reported outcomes • Anorexia • Chronic Myeloid Leukemia • CNS Disorders • Depression • Hematological Malignancies • Leukemia • Mood Disorders • Palliative care

Treatment free remission after asciminib (ABL001) based therapy in chronic Phase chronic myeloid leukemia (CP-CML) patients who relapsed after a prior attempt at TKI discontinuation-h jean khoury cure CML consortium study HJKC3-0003 (ASH 2025) - "This trial will use any of the following (based on patient/physician preference) during the consolidation treatment phase: asciminib 40 mg PO daily plus imatinib (maximum dose of 400 mg PO once daily), asciminib 40 mg PO bid plus nilotinib (maximum dose of 300 mg bid), asciminib 80 mg PO daily plus dasatinib (maximum dose of 100 mg daily), asciminib 80 mg PO daily. This is the first report of asciminib use to attempt 2 nd TFR. The combination was well tolerated, and patients were able to complete the combination phase. Preliminary results suggest feasibility and potential to increase cure for CML."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

Asciminib versus second generation TKI in newly diagnosed chronic Phase chronic myeloid leukemia: A meta analysis (ASH 2025) - "Two randomized controlled trials including 868 patients (484 receiving asciminib and 384 receiving second-generation TKIs) were included. At 12 weeks, early molecular response (BCR::ABL1 <10%) was achieved in 90% of patients on asciminib compared to 82% in the 2G-TKI group (RR 1.11, 95% CI 1.04–1.17; I²=0). Complete molecular response (BCR::ABL1 ≤1%) was seen in 74.5% of asciminib-treated patients versus 60.7% with 2G-TKIs (RR 1.19, 95% CI 0.95–1.48; I²=84%)."

Retrospective data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Thrombocytopenia • ABL1

Overcoming asciminib resistance by targeting compound BCR::ABL1 mutations in chronic myeloid leukemia (ASH 2025) - "Selected candidate compounds demonstrating efficacy were validated across a panel of CML models, including Ba/F3 cells expressing wild-type BCR::ABL1, the T315I mutant (Ba/F3 T315I), and compound mutations (Ba/F3 PR: Y253H, E255K, and T315I), as well as K562 cells and their drug-resistant derivatives, K562 imatinib-resistant (K562 IR) and K562 ponatinib-resistant (K562 PR). CML cells with compound BCR::ABL1 mutations exhibited resistance to asciminib and, in part, to ponatinib, while bortezomib and selinexor retained efficacy in these resistant cells. Olverembatinib effectively suppressed proliferation and induced apoptosis in ABL TKI-resistant CML cells. The combination of olverembatinib and selinexor synergistically induced apoptosis and suppressed proliferation, offering a promising approach for overcoming TKI-resistant CML with compound mutations."

IO biomarker • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1 • CASP3 • CASP7

A case of co-mutation of SF3B1 and BCR::ABL1 demonstrating an MDS-phenotype (ASH 2025) - "Bone marrow sampling repeated 3 months after starting asciminib showed minimal change in cellularity and erythroid predominance...To our knowledge, this is the first report mapping the clonal architecture of a case of concurrent CML and SF3B1-mutated MDS using single-cell DNA sequencing. These findings not only provide novel insight into lineage restriction and clonal dominance but also reveal how a concurrent mutation can mask the classic disease phenotype of CML."

Clinical • Chronic Myeloid Leukemia • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Prostate Cancer • Solid Tumor • ABL1 • SF3B1

Real-world treatment patterns, outcomes, and unmet needs in patients with ph+ ALL receiving tyrosine kinase inhibitors in the United States: Emerging trends and the role of asciminib-based combinations (ASH 2025) - "Anytime during the follow-up period, 67%received dasatinib, 35% ponatinib, 24% imatinib, 13% nilotinib, 6% bosutinib, and 66 (2%) asciminib-based therapy.Based on the index TKI, treatment patterns evolved over time, with important shifts between 2016 and2024...Asciminib was given ascombination therapy (82%) with corticosteroids (76%), chemotherapy (64%), inotuzumab ozogamicin(16%), and blinatumomab (15%). This real-world study described evolving patterns in the management of pts with Ph+ ALL... This real-world study described evolving patterns in the management of pts with Ph+ ALL. Inrecent years, increased use of ponatinib and immunotherapy has been observed alongside a decline inuse of dasatinib and imatinib. Despite therapeutic advances, many pts experienced clinical eventsassociated with TKI-related conditions, and one-third had disease relapse."

Clinical • HEOR • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Ischemic stroke • Leukemia • Myocardial Infarction • Respiratory Diseases

Asciminib and pregnancy in CML: Preliminary human data and clinical implications from 47 reported outcomes (ASH 2025) - "In the paternal exposure group, 8 men were receiving ASC asmonotherapy at the time of conception, while 5 were treated with ASC in combination with nilotinib orimatinib...In most cases, ASC hadbeen discontinued during the first trimester, often between 4 and 9W, with daily doses ranging from 20to 120 mg, and one ASC 40 QD+imatinib 400 mg...However, contraception is advised for women on ASC, especially if previouslyfailing other treatments; no contraception is needed for men. The presentation will provide updatedclinical details, including CML management during gestation and reproductive outcomes, offeringinsights to improve patient counseling, support informed reproductive choices, and guide personalizedtreatment."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Pneumonia • Respiratory Diseases • ABL1

Asciminib for newly diagnosed chronic myeloid leukemia: Results from A phase II trial (ASH 2025) - "A 71-year-oldpatient with a previous medical history of hypertension developed G5 acute coronary syndrome after 2.5months of asciminib therapy.Overall, 5 of 50 patients (10%) discontinued asciminib after a median of 7.6 months (range, 0.5-16.6) dueto 1) a G3 subacute brain stroke, switched to bosutinib; 2) a G2 and G3 pancreatitis in one patient each,both switched to dasatinib; 3) a G5 acute coronary syndrome (NSTEMI) with cardiogenic shock in a 71-year-old male w; 4) a loss of CCyR after 11.4 months of therapy with the emergence of A337T and F497Lmutations with subsequent switch to ponatinib. The 6-month rates of FFS, EFS, and OS were 93%, 97%,and 97%, respectively.ConclusionThis interim analysis showed very good response rates with asciminib in ND CML after a short follow-upwith MMR and deep molecular response rates of 64% and 42% by 6 months, respectively. Adverseevents, including gastrointestinal, as well as one fatal cardiovascular event, were observed."

P2 data • Acute Coronary Syndrome • Chronic Myeloid Leukemia • Coronary Artery Disease • Hematological Malignancies • Hypertension • Leukemia • Musculoskeletal Pain • Pancreatitis • ABL1

Outcomes of patients with chronic myeloid leukemia receiving second-line therapy after failure of frontline second-generation tyrosine kinase inhibitor (ASH 2025) - "The 10-year EFS, TFS, and OS rates with 1L were 57%, 100%,and 79%, respectively.2L consisted of imatinib in 74 pts (27%), bosutinib in 64 (23%), nilotinib in 57 (21%), dasatinib in 43 (15%),ponatinib in 31 (11%), asciminib in 6 (2%), and investigational drug in 1 (1%). Of 65 pts withtranscripts <0.1%, 59 (91%) maintained their response.The estimated 10-year EFS, TFS, and OS rates on 2L therapy were 67%, 87%, and 71%, respectively.ConclusionOverall, 2L after 1L 2G-TKI resulted in cytogenetic remissions in approximately 80% of the pts andmolecular remissions in more than 60% of the pts. Response rates were significantly higher in pts treatedwith a 3G-TKI compared to a 2G-TKI in the second line."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

BCR::ABL1/GUSB halving times predict molecular response to asciminib at 18 months (ASH 2025) - "To date,however, no comparative analysis of the utility of different reference genes to assess early responsekinetics has been performed.We have evaluated the utility of halving times derived using GUSB and ABL1 as reference genes inFASCINATION, a multicenter, prospective, open-label, interventional phase II trial designed to evaluatethe efficacy and tolerability of asciminib following <6 weeks treatment with other TKIs or <4 weeks ofhydroxyurea. Established GUSB conversionfactors (CF) derived by sample exchange were essentially indistinguishable from those derived using thepanel [Lab 1: existing CF (0.99) / panel CF (1.02) = 0.97; Lab 2: existing CF (1.57) / panel CF (1.40) = 1.12,thus validating the panel to standardize GUSB measurements.We conclude that halving times over the first 3 months of asciminib treatment using GUSB or ABL1 aswell as IS levels at 3 months are all predictive of molecular response at 18 months, but the predictivevalue of GUSB halving times..."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

High rates of deep molecular response (DMR) in patients (pts) with chronic myeloid leukemia in chronic Phase (CML-CP) who have not achieved dmr after ≥1 year of prior imatinib (IMA) in the asciminib (ASC) monotherapy arm of the Phase 2 ASC4MORE study (ASH 2025) - P2 | "In the phase 2ASC2ESCALATE study (NCT05384587), second-line ASC demonstrated high molecular response rates anda favorable safety profile, consistent with established ASC data across tx lines.The ASC4MORE study (NCT03578367) initially compared ASC 40 or 60 mg once daily (QD) add-on to IMA400 mg QD vs continued IMA 400 mg QD vs switch to nilotinib (NIL) 300 mg twice daily in pts with CML-CPnot achieving MR4 with ≥1 year of 1L IMA. No new or worsening safety signalswere observed compared with prior ASC studies and overall QOL improved or remained stable in mostpts. Results support early switching to ASC as an effective strategy to achieve DMR while maintainingfavorable safety/tolerability and QOL."

Clinical • Monotherapy • P2 data • Anorexia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hypertension • Infectious Disease • Insomnia • Leukemia • Musculoskeletal Pain • Nephrology • Pancreatitis • Pulmonary Disease • Sleep Disorder

Improved long-term tolerability with asciminib (ASC) vs investigator-selected (IS) tyrosine kinase inhibitors (TKIs) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Week 96 exploratory analysis of the phase 3 ASC4FIRST trial (ASH 2025) - P3 | "Wereport exploratory post hoc analyses, including an innovative analysis of AE-free days, further evaluatingthe tolerability of ASC vs IS-TKI (imatinib [IMA]/2G TKIs) by the wk 96 analysis cutoff (Oct 22, 2024).MethodsAdults with newly diagnosed CML-CP were randomized 1:1 to receive ASC or IS-TKI (at label dose),stratified by ELTS risk category and prerandomization IS-TKI (IMA/2G TKIs)...Dose adjustment and/or interruption due to grade ≥3 nonhematologic AEs occurred in17.0% vs 8.1% of pts with ASCIMA vs IS-TKIIMA and 11.0% vs 17.6% with ASC2G vs IS-TKI2G.Pts with ASC vs IS-TKIs had a higher median percentage of AE-free days by wk 96 (ASCIMA [15.7%] vs IS-TKIIMA [3.5%]; ASC2G [22.6%] vs IS-TKI2G [4.3%]) and vs individual 2G TKIs (nilotinib [13.5%]; dasatinib[4.2%]; bosutinib [0.1%]) in this arm...Effective relative dose intensity (>90%) was higher with ASC vs IS-TKIs, with generally fewer ptsrequiring dose reduction, interruption, or discontinuation. These results..."

Clinical • P3 data • Chronic Myeloid Leukemia • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Beyond survival in chronic myeloid leukemia: A systematic review of secondary malignancies in the era of tyrosine kinase inhibitors (ASH 2025) - "Eligible studies were those reporting the incidence of SMs in adults withchronic-phase CML treated with TKIs, including imatinib, dasatinib, nilotinib, bosutinib, ponatinib, andasciminib...Data on bosutinib (n=2) and ponatinib (n=1) were limited, while asciminib was notreported in any study... This reviewidentified a notable incidence of SMs, particularly involving prostate, colorectal, lung, and lymphoidcancers. While some variability in cancer types was observed across studies, no consistent associationcould be established between TKI generation or treatment duration and SMs risk.SM development wasassociated with poor prognosis and increased mortality, highlighting the need for proactive surveillance.Large-scale prospective studies are needed to clarify causality, define long-term safety, and informsurvivorship strategies."

Review • Breast Cancer • Chronic Myeloid Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

The impact of NR1I2 gene polymorphism and body weight on asciminib pharmacokinetics in patients with chronic myeloid leukemia (ASH 2025) - "The initial dose of asciminib may require adjustment based on NR1I2 genotype and patientbody weight. As the 80 mg QD regimen is more influenced by body weight than by the tested geneticpolymorphisms, underweight female patients treated with this regimen may exhibit higher drugexposure."

Clinical • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABCB1 • ABCC2 • ABCG2 • CYP3A4 • NR1I2

Dosing variability of tyrosine kinase inhibitors in chronic myeloid leukemia (ASH 2025) - "The latest TKI therapy included dasatinib, imatinib, bosutinib, nilotinib, asciminib andponatinib in 34%, 29%, 18%, 11%, 6% and 2% of the patients, respectively. Most importantly, we note that more than 50% of the patientsare on a lower dose TKI in the later line settings without compromising outcomes, highlighting that thereis room for optimization of TKI dosing strategy in CP-CML for improved patient tolerance whilemaintaining outcomes. Larger registry studies are needed to better understand prescription practices ofTKIs in CP-CML."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

The humanistic burden of patients with chronic myeloid leukemia (CML) treated with first line (1L) tyrosine kinase inhibitors (TKIs) (ASH 2025) - "Adultsreceiving 1L TKIs (imatinib, dasatinib, nilotinib, bosutinib) for ≥3 months (mos) were eligible to participate; asciminib in 1L was not yet approved at study start. Our real-world study demonstrates pts with CML treated with 1L TKIs in the US experience chronic AEscontributing to worse HRQoL, including physical and mental health, as well as work impairment. Thisfinding of impaired work productivity due to CML is particularly significant in the context of employer-provided health insurance in the US. While most patients discussed AEs with physicians early in theirdisease course, only half discussed AEs at every visit and two-thirds were satisfied with their discussions.In addition, some patients delayed or avoided reporting AEs due to internal barriers."

Clinical • Chronic Myeloid Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Musculoskeletal Pain

Quantitative real-time polymerase chain reaction coupled with high-resolution melting (HRM) for simultaneous detection and quantification of four isoforms of BCR::ABL1 (ASH 2025) - "Atypical transcripts have also been described, including e13a3/e14a3 (p203),which has been anecdotally linked to asciminib resistance...Quantitative values obtained with our approach correlated tightly with the standardized Qiagenipsogen IS assay (r = 0.998; median absolute difference = 0.02%).ConclusionThe BloodHound assay is sensitive and accurate, and by simultaneously quantifying four clinicallysignificant BCR::ABL1 transcripts, it has the potential to significantly streamline clinical workflows,enhance diagnostic precision, and offer deeper insights into CML clonal dynamics. Both RT-qPCR andHRM are compatible with standard laboratory equipment, facilitating implementation and widespreadclinical adoption."

Polymerase Chain Reaction • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1