CML Session Summaries from EHA2026 Congress

Oral Session: Chronic Myeloid Leukemia – Clinical

Chairs: Tim Henrik Brümmendorf (Aachen) and Delphine Réa (Paris)

This session showcased important advances in the clinical management of CML, with a strong focus on improving molecular responses, expanding opportunities for treatment-free remission (TFR), and developing new therapeutic options for patients across different treatment settings. Long-term follow-up data from ASC4FIRST reinforced the emerging role of asciminib as a frontline therapy, while two independent studies demonstrated that a second TFR attempt is achievable in selected patients. Additional presentations explored novel strategies to deepen molecular responses through asciminib-based combination therapy and highlighted encouraging early results from the highly selective next-generation BCR::ABL1 inhibitor ELVN-001. 

Our key takeaways from the presentations:

Presentation 1:

ASC4FIRST week 144 analysis: Continued superior efficacy and favourable safety of asciminib versus investigator-selected tyrosine kinase inhibitors in newly diagnosed chronic myeloid leukemia

Speaker: Timothy Hughes (Adelaide)

“Asciminib continues to demonstrate a favourable benefit-risk profile compared with current standard-of-care TKIs. The difference in MR4.5 at three years may prove particularly important as a pathway towards treatment-free remission.”– Timothy Hughes

Key points:

• Superior molecular responses: At 144 weeks, asciminib maintained significantly higher rates of major molecular response (MMR) and deep molecular response compared with both imatinib and investigator-selected second-generation TKIs. 
• Higher rates of deep molecular remission: Deep molecular responses continued to improve with longer treatment duration. At week 144, MR4.5 rates reached 41% with asciminib compared with 29% for second-generation TKIs, reinforcing the potential of asciminib to increase future treatment-free remission opportunities.
• Improved treatment persistence: More patients remained on asciminib therapy after three years compared with either imatinib or second-generation TKIs. Lower rates of treatment failure and fewer discontinuations due to adverse events contributed to superior long-term treatment retention.
• Favourable resistance profile: No new BCR::ABL1 mutations emerged during the third year of follow-up. Importantly, previously observed asciminib-resistant mutations remained manageable through subsequent treatment with second-generation TKIs.
• Future TFR potential: The study is ongoing, and analyses to assess the potential for TFR eligibility and success are planned. 
   

Presentation 2:

Ponatinib consolidation and discontinuation in chronic myeloid leukemia patients after failed first treatment-free remission attempt: Updated TFR outcomes and CHIP mutation analysis from ReStop Trial

Speaker: Gonzalo Carreño Gómez-Tarragona (Barcelona)

“Ponatinib consolidation achieved high TFR rates in patients who had failed previous TKI discontinuation attempts.”– Gonzalo Carreño Gómez-Tarragona

Key points:

• High rates of second treatment-free remission: Ponatinib consolidation followed by a second discontinuation attempt resulted in encouraging TFR outcomes in patients who had previously relapsed after their first stop attempt. One year after ponatinib discontinuation, 68.2% of patients remained treatment-free, exceeding outcomes previously reported in many second-attempt TFR studies.
• Effective molecular consolidation strategy: Patients received two years of ponatinib consolidation before re-attempting treatment discontinuation. The findings suggest that intensifying therapy with a potent TKI may help restore durable treatment-free remission in selected patients.
• No disease progression observed: No cases of progression to advanced-phase disease were reported during the study. Most patients who successfully completed the consolidation phase maintained molecular remission throughout the first year of treatment discontinuation.
• Manageable but important safety considerations: Adverse events were consistent with the established ponatinib safety profile, including hypertension and vascular events. These findings highlight the need for careful patient selection and cardiovascular risk assessment when considering this strategy.
• Potential impact of CHIP mutations: Patients carrying CHIP mutations appeared more likely to maintain TFR than non-carriers, although the differences were not statistically significant due to the small sample size. The observation warrants further investigation in larger cohorts.
• No increased cardiovascular risk associated with CHIP: Importantly, CHIP mutations were not associated with a worse cardiovascular or overall safety profile in ponatinib-treated patients. This provides reassurance that CHIP status alone should not necessarily exclude patients from this approach.
   

Presentation 3:

High rates of successful second stop attempts in patients with chronic myeloid leukemia: Results of the NAUT trial
Speaker: Susanne Saussele (Mannheim)

“The NAUT trial demonstrates that a relevant proportion of patients after a second discontinuation can achieve successful TFR. Longer retreatment before a second stop attempt may be an important contributor to success.”– Susanne Saussele

Key points: 

• Second TFR attempts can be successful: The NAUT trial demonstrated that a substantial proportion of patients can successfully discontinue treatment after a previous unsuccessful stop attempt. Molecular recurrence-free survival reached 58% at 12 months, exceeding the study’s predefined expectations.
• Extended retreatment may improve outcomes: Patients underwent two years of nilotinib consolidation before attempting treatment discontinuation again. The findings suggest that prolonged retreatment and re-establishment of stable deep molecular responses may be critical factors for successful second TFR attempts.
• Rapid regain of response after relapse: Most molecular relapses occurred early, with a median time to relapse of just over three months. Nearly all patients who restarted therapy rapidly regained deep molecular responses, confirming the safety of close molecular monitoring.
• No new safety signals identified: The safety profile observed during nilotinib treatment was consistent with previous experience and no unexpected adverse events emerged. No disease progression or CML-related deaths were reported during the study.
• Cardiovascular events require monitoring: More than 40% of patients experienced cardiovascular adverse events, although most were low-grade and largely related to hypertension. Serious cardiovascular complications remained relatively uncommon in this carefully selected population.
• A realistic option for selected patients: The results support offering a second treatment discontinuation attempt to appropriate patients who regain stable deep molecular responses. These findings add to growing evidence that TFR may remain achievable even after an initial unsuccessful attempt.

Presentation 4:

Efficacy and safety of adding low-dose tyrosine kinase inhibitors for patients with CML who don't achieve optimal response or a deep molecular remission 
(ALERT-CML)

Speaker: Jay Yang (Chicago)

“The addition of low-dose TKI to asciminib was feasible and safe in patients who failed to achieve deep molecular remission. Combination therapy improved responses in 66% of patients.”– Jay Yang

Key points: 

• Strong frontline activity with asciminib: Asciminib monotherapy continued to generate rapid and deep molecular responses, with 42% of patients achieving MR4 at 12 months. Responses continued to deepen over time, supporting the growing body of evidence for asciminib as an effective frontline therapy.
• Combination therapy for suboptimal responders: Patients with treatment failure, warning responses, or insufficient molecular depth were offered low-dose TKI therapy in addition to asciminib. This strategy aimed to overcome residual disease and further enhance molecular responses.
• Improved molecular responses in most patients: Two-thirds of patients receiving combination therapy achieved improved molecular responses after the addition of low-dose dasatinib. Importantly, no patient experienced deterioration of their molecular response following treatment intensification.
• Potential to increase deep remission rates: Both patients who entered the study arm because they had not achieved MR4.5 after two years of asciminib subsequently reached MR4.5 after low-dose TKI addition. These findings suggest a possible role for combination therapy in expanding future TFR eligibility.
• Favourable safety profile maintained: Combination treatment was generally well tolerated, with most adverse events being mild. No cardiovascular events, thrombotic complications, pleural effusions, or QT prolongation signals were observed during follow-up.
• Promising strategy requiring longer follow-up: Although patient numbers remain small and follow-up is relatively short, the results provide early evidence that asciminib-based combination therapy may benefit patients with slower or suboptimal molecular responses.

Presentation 5: 

ENABLE: Updated efficacy and safety results of ELVN-001, a novel selective ATP-competitive inhibitor of BCR::ABL1 in patients with previously treated CP-CML

Speaker: Dennis Kim (Toronto)

“Encouraging MMR rates were observed even in heavily pre-treated patients and after asciminib failure.” – Dennis Kim

Key points: 

• Highly selective next-generation inhibitor: ELVN-001 is a highly selective ATP-competitive inhibitor of BCR::ABL1 that minimizes off-target kinase inhibition. Its unique binding properties may help reduce toxicities associated with currently available TKIs and offer activity against several resistance mutations, including those emerging after allosteric inhibition.
• Favourable safety and tolerability profile: Longer-term follow-up confirmed a favourable safety profile, with only around 6% of patients discontinuing treatment because of adverse events. Rates of arterial occlusive events were low, and no new safety concerns emerged despite treatment in a heavily pre-treated population.
• Encouraging efficacy in heavily pre-treated patients: Among patients who had not achieved MMR prior to ELVN-001 treatment, 48% attained MMR, while all patients who entered the study with MMR maintained their response. Responses occurred rapidly, with many patients achieving MMR within the first 24 weeks of therapy.
• Deep molecular responses continued to develop: At week 24, approximately 30% of patients receiving the biologically active 80 mg once-daily dose achieved MR4. Molecular responses were either maintained or improved over time, with no evidence of worsening response during treatment.
• Activity after asciminib failure: ELVN-001 demonstrated clinically meaningful activity in patients previously treated with asciminib. MMR rates reached 67% in patients who had failed asciminib after one or two prior lines of therapy and remained approximately 33% even in patients who had received asciminib in later treatment lines.
• Advancing towards Phase 3 development: Based on safety, pharmacokinetic and pharmacodynamic analyses, 80 mg once daily was selected as the optimal biological dose. The pivotal Phase 3 ENABLE-2 study is expected to begin in the second half of 2026.