Treatment-free remission is one of the most important goals of CML treatment but so far, the best treatment to reach this aim is still undefined, even though it is widely accepted that a sustained DMR is the prerequisite to discontinue TKI. Here we report on the depth of the molecular response, the first co-primary end point of the SUSTRENIM study, in a cohort of newly diagnosed CP-CML patients randomized 1:1 to be treated with nilotinib or with imatinib followed by switching to nilotinib in absence of optimal response. Of the 448 enrolled patients, 228 and 220 were randomized to the nilotinib (NIL) and imatinib (IM) arms, respectively, and followed for a median of 45.9 months. Eighty-two (37.2%) of the 220 patients on the IMarm did not fulfill the ELN criteria for optimal response of treatment and switched to nilotinib therapy. At the 24 months of follow-up, 107 of the 448 patients reached an MR4.5 response with a significantly higher frequency within the patients on the nilotinib arm (65 vs 42; p = 0.02). The analysis of the first primary endpoint indicates that, despite the early switch in the IM-randomized patients, NIL therapy is more effective to induce DMR.

Real world outcomes of patients with CML-CP treated with tyrosine kinase inhibitors from the h. jean khoury cure CML consortium (HJKC3)

A machine learning approach identifies a transcriptomic signature predicting treatment-free remission in chronic myeloid leukemia

Supersaturation of self-nanoemulsifying drug delivery systems: Correlation between equilibrium solubility and supersaturation concentration, effect on droplet size and impact of polymer addition.

6501 Background: ASC, the first BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket, recently received FDA Accelerated Approval for newly diagnosed CML-CP based on major molecular response (MMR) rates in the ASC4FIRST trial (NCT04971226). We present results from ASC4START (NCT05456191), with the primary objective of assessing the tolerability of ASC vs second-generation tyrosine kinase inhibitor NIL in patients (pts) with newly diagnosed CML-CP. Methods: Adults were randomized 1:1 to receive ASC 80 mg once daily or NIL 300 mg twice daily, stratified by ELTS risk category. The primary endpoint is TTDAE. Events included AEs leading to treatment (tx) discontinuation and deaths due to AEs. Secondary endpoints include molecular response and safety. Results: Pts were recruited by 120 participating sites across 24 countries and randomized to ASC (n=284) or NIL (n=284). Two pts who did not receive NIL were excluded from safety analyses. Median follow-up was 9.7 mo. At cutoff (Sep 3, 2024), 10.9% and 17.3% of pts discontinued ASC and NIL, respectively, most commonly due AEs (4.9% vs 11.6%) and unsatisfactory therapeutic effect (2.5% vs 2.8%). The study met its primary endpoint, showing statistically significant difference in TTDAE in favor of ASC with a cause-specific hazard ratio of 0.45 (95% CI, 0.25-0.81; P =.004). Fewer pts discontinued due to AEs with ASC (16/284 [5.6%]) vs NIL (34/282 [12.1%]). There were 3 deaths on study due to AEs (ASC: cardiac arrest and suicide, n=1 each; NIL: cardiac arrest, n=1). Median duration of exposure was 39.1 wk with ASC vs 38.0 wk with NIL. Mean relative dose intensity was 94.8% vs 92.6%, respectively. Any-grade AEs occurred in 80.3% of pts with ASC vs 86.5% with NIL. Grade ≥3 AEs occurred in 25.0% and 31.9% of pts, respectively. AEs leading to dose adjustment/interruption occurred in 24.3% of pts with ASC vs 30.1% with NIL. Most frequent any-grade AEs (≥10%) with ASC vs NIL were thrombocytopenia (15.1% vs 13.8%), headache (10.2% vs 13.1%), myalgia (10.2% vs 8.2%), rash (8.5% vs 16.3%) and increased alanine aminotransferase (3.2% vs 12.4%). AEs of special interest included arterial occlusive events (0.7% vs 2.1%), acute pancreatitis (clinical events; 0.4% vs 2.5%), and hepatotoxicity (including laboratory terms; 8.1% vs 24.8%). BCR::ABL1 IS ≤10% (89.8% vs 82.0%), BCR::ABL1 IS ≤1% (69.0% vs 52.5%), MMR (22.9% vs 10.2%), MR 4 (4.6% vs 1.1%), and MR 4.5 (2.5% vs 0.4%) rates by wk 12 were higher with ASC vs NIL. Conclusions: The study met the primary endpoint with ASC showing significantly superior tolerability vs NIL based on TTDAE. The study is ongoing with additional analyses planned for tolerability and efficacy. The findings further support the potential for ASC to be a preferred therapy for newly diagnosed CML-CP, allowing more pts to meet tx goals without requiring tx switch. Clinical trial information: NCT05456191 .

Assessment of Transitioning from High-Potency to Low-Potency Inhibitors in Chronic Myeloid Leukemia (CML) Patients: The Downgrading-Impact Project, a CML Campus Study

Results of the Molecular Response Evaluation and TKI Dose Adjustment in Chronic Myeloid Leukemia Patients in Prospective Study of Reduction and Discontinuation Treatment of TKI (READIT)

Objective: To analyze the treatment-free remission (TFR) outcomes in patients with chronic myeloid leukemia (CML) treated sequentially with nilotinib (NIL) after achieving deep molecular response (DMR) to imatinib (IM). Methods: Retrospectively enrolled 103 CML patients from 6 hematological centers in Henan Province who chose sequential NIL therapy or continued IM therapy after achieving DMR to first-line IM from June 2, 2013 to August 30, 2022. Among them, 42 cases were treated with sequential NIL and 61 cases continued IM therapy. The 42 patients in the sequential NIL group were further divided into 3 subgroups based on the duration of DMR at switching to sequential NIL therapy: Group 1 (17 cases): DMR duration<12 months at switching to sequential NIL therapy; Group 2 (8 cases): DMR duration≥12 months to<24 months at switching to sequential NIL therapy; Group 3 (17 cases): DMR duration≥24 months at switching to sequential NIL therapy. Follow-up ended on January 9, 2024, with a median follow-up of 40 (16, 91) months for the sequential NIL group and 49 (21, 123) months for the continuous IM group. Survival curves were plotted using the Kaplan-Meier method and the log-rank test was performed to compare the TFR rates between groups. Results: There were 19 males and 23 females with a median age [M (Q1, Q3)] of 43 (31, 50) years in the sequential NIL group. There were 32 males and 29 females with a median age of 41 (31, 50) years in the continuous IM group. Kaplan-Meier survival curve analysis showed that the TFR rate was higher in the sequential NIL group than in the continuous IM group (88.1% vs 63.9%, P=0.005). The results of subgroup analysis showed that the TFR rates in Group 1, Group 2 and Group 3 were 94.1%, 87.5% and 82.4%, respectively, with no statistically significant differences (all P>0.05).The TFR rate in Group 1 was higher than in the continued IM group (P=0.017), and there were no statistically significant differences in Group 2 and Group 3 compared with the continuous IM group(all P>0.05). Conclusion: Sequential NIL therapy after achieving DMR with IM therapy can improve the TFR rate in CML patients, especially in those with DMR duration<12 months before switching to sequential NIL therapy.

Nilotinib (NIL) is a prescription medication employed in the treatment of specific types of leukemia, namely chronic myelogenous leukemia (CML). The determination of NIL levels in patients undergoing treatment for CML is of paramount importance for effective management of treatment and toxicity. Also, monitoring and controlling its level in wastewater sources could help scientists to identify potential hotspots of contamination and take appropriate measures to mitigate their impact on the environment and public health. This study presents a D-µ-SPE technique utilizing two MOFs as adsorbents for the efficient detection of nilotinib in plasma and wastewater samples for the first time. Two highly effective MOFs, MIL-101(Fe) and MIL-53(Al), were synthesized and applied as dispersive micro-solid phase extraction (D-µ-SPE) adsorbents for the extraction of nilotinib coupled with HPLC-UV in a short time of analysis. Experimental parameters affecting extraction efficacy such as adsorbent amount, ionic strength, pH value, adsorption-desorption time and type of elution solvent, were optimized. Under optimal experimental conditions, the linear dynamic was achieved in the range of 0.25-5.00 µg/mL in human plasma and 0.01-0.20 µg/mL in wastewater. The extraction recovery was in the range of 89.18-91.53% and 94.39-99.60% for nilotinib and MIL-101(Fe) and also 91.22-97.35% and 98.14-100.78% for nilotinib and MIL-53(Al) from human plasma and wastewater respectively. HPLC-UV determination of nilotinib after the D-µ-SPE method showed acceptable accuracy and precision in both plasma and wastewater. In comparison between the two adsorbents, the extraction procedure was easier and faster with MIL-53(Al) as the adsorbent.

Retrospective Study to Evaluate Probability of MR4 Maintenance Following Frontline Nilotinib Dose De-Escalation after MR4 Achievement in the Patients with Chronic Myeloid Leukemia in Chronic Phase

Efficacy of Frontline Treatment with Initial Low-Dose Tyrosine-Kinase Inhibitors in Elderly Patients with Chronic Myeloid Leukemia: A “Campus CML” Study

In Vitro Evidence of Synergistically Enhanced Efficacy of Axitinib When Combined with Asciminib in T315I Mutated Chronic Myeloid Leukemia

Baseline Features, Treatment Choice and Early Frontline TKI Permanent Discontinuation in Younger Patients with Chronic Myeloid Leukemia: A “Campus CML” Study

Asciminib (ASC) in Combination with Imatinib (IMA), Nilotinib (NIL), or Dasatinib (DAS) May be a Potential Treatment (Tx) Option in Patients (Pts) with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase (Ph+ CML-CP/AP): Final Results from the Asciminib Phase 1 Study

Treatment Free Remission after Nilotinib Plus Peg-Interferon Alpha Induction and Peg-Interferon Alpha Maintenance Therapy for Newly Diagnosed Chronic Myeloid Leukemia Patients; The Tiger Trial

Full Treatment-Free Remission Outcome in Patients with Chronic Myeloid Leukemia in Chronic Phase Following One Year of Nilotinib De-Escalation: 96-Week Update of Dante Study

Asciminib (ASC) Add-on to Imatinib (IMA) Demonstrates Sustained High Rates of Ongoing Therapy and Deep Molecular Responses (DMRs) with Prolonged Follow-up in the ASC4MORE Study

Asciminib Enhances Its Treatment Efficacy Synergistically in the Treatment of Chronic Myeloid Leukemia Harboring ABL1 Kinase Domain Mutation When Combined with a Reduced Dose of Ponatinib, Dasatinib, or Bosutinib, but Not with Nilotinib or Imatinib

Nilotinib alleviates paraquat-induced hepatic and pulmonary injury in rats via the Nrf2/Nf-kB axis

Remodeling of the liver fibrosis microenvironment based on nilotinib-loaded multicatalytic nanozymes with boosted antifibrogenic activity