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Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received ≥ 2 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40 mg twice-daily or bosutinib 500 mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, n = 13; bosutinib, n = 3) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.

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INTRODUCTION: Leukemic stem cells (LSCs) are the transcriptionally low/silent cells which are resistant to the tyrosine kinase inhibitor. These have been found to play a pivotal role in disease relapse in chronic myeloid leukemia (CML) cases. The present study evaluated the correlation of absolute CML-LSC count in the peripheral blood (PB) at diagnosis and achievement of major molecular response (MMR) at 12 months in patients of CML-CP. METHODS: This was a prospective, observational, non-interventional single center study including newly diagnosed adult (>18 yrs) CML-CP patients. Absolute CD26 + CML-LSC quantification was done by multiparametric flow cytometry. Patients were treated with Imatinib treatment and subsequently monitored at 3-month intervals for BCR::ABL transcript levels. MMR was defined as a BCR::ABL1 transcript level of less than 0.1% on international scale. RESULTS: A total of 89 patients were enrolled in the study out of which 40.5% achieved MMR at 12 months. There was a significant difference in the median absolute CML-LSC count of the patients who achieved MMR at 12 months as compared to those who did not (58.5 vs 368.1 cells/µL; p value <0.001). Using a ROC analysis, a count of <165.69 CML LSC/µL was identified to have a sensitivity of 83.8% and specificity of 72.4%, in predicting the MMR at 12 months. CONCLUSION: Absolute CML-LSC count at diagnosis in the PB predicts the MMR achievement at 12 months. An absolute count of less than 165 cells/µL is highly predictive of achieving MMR at 12 months.

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BACKGROUND: Dasatinib is a BCR::ABL1 tyrosine kinase inhibitor approved as frontline therapy at a 100 mg daily for chronic myeloid leukemia in chronic phase (CML-CP). The use of a lower dose of dasatinib (50 mg daily) has demonstrated better tolerance and improved outcomes compared with the standard dose. Here, we report the updated results in a large cohort with a 5-year follow-up. PATIENTS AND METHODS: Patients with newly diagnosed CML-CP were eligible. Entry and response-outcome criteria were standard. Dasatinib was given as 50 mg orally daily. RESULTS: Eighty-three patients were included. At 3 months, 78 (96%) patients achieved BCR::ABL1 transcripts (IS) ≤10%, and at 12 months, 65 (81%) patients achieved BCR::ABL1 transcript (IS) ≤0.1%. The cumulative incidence of complete cytogenetic, major molecular, and deep molecular responses at 5 years were 98%, 95%, and 82%, respectively. Rates of failures due to resistance (n = 4; 5%) and toxicity (n = 4; 5%) were low. The 5-year overall survival was 96% and event-free survival 90%. No transformations to accelerated or blastic phase were observed. Grade 3 to 4 pleural effusions developed in 2% of patients. CONCLUSION: Dasatinib 50 mg daily is an effective and safe treatment for newly diagnosed CML-CP.

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Chronic myeloid leukemia (CML) is characterized by the fusion gene BCR-ABL1 which encodes aberrantly functioning tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKI) is a landmark of CML management and the main goal is to achieve major molecular response (MMR) which is defined as BCR-ABL1IS ≤ 0.1 % at 12 months of therapy. The aim of this study is to analyze histologic features of bone marrow (BM) in CML patients at the time of diagnosis and compare it to the level of BCR-ABL1IS transcript at 3 (BCR-ABL1IS ≤10 % early molecular response; EMR) and 12 months (MMR) as well as to so called molecularly undetectable leukemia (MUL) to see weather bone marrow morphology can be of value in predicting achievement molecular response milestones. Thirty-two bone marrow biopsies of CML patients, prior TKI therapy, were re-evaluated and CD34 immunohistochemistry was performed to examine microvessel density (MVD) and microvessel area (MVA) and subsequently compared it to the level of BCR-ABL1IS transcript. This study showed statistically significant association between BM hypercellularity and EMR (p = 0.048) and MUL (p = 0.034), peri-trabecular adipocyte distribution and EMR and MUL (p = 0.027 and p = 0.011, respectively), MMR and bone marrow fibrosis (p = 0.029), loose megakaryocyte clustering and EMR and MUL (p = 0.004 and p = 0.018, respectively), absence of naked nuclei and MUL (p = 0.033) but there was no statistically significant association with vascular parameters. These results suggest that some bone marrow morphologic features prior TKI therapy might be indicators of favorable molecular response.

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The achievement of major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) is a milestone in the therapeutic management of patients with newly diagnosed chronic myeloid leukemia (CML). We analyzed the predictive value of gene expression levels of ESPL1/Separase, PTTG1/Securin and PTTG1IP/Securin interacting protein for MMR achievement within 12 months. Relative expression levels (normalized to GUSB) of ESPL1, PTTG1 and PTTG1IP in white blood cells of patients (responders n = 46, non-responders n = 51) at the time of diagnosis were comparatively analyzed by qRT-PCR. 3D scatter plot analysis combined with a distance analysis performed with respect to a commonly calculated centroid center resulted in a trend to larger distances for non-responders compared to the responder cohort (p = 0.0187). Logistic regression and analysis of maximum likelihood estimates revealed a positive correlation of distance (cut-off) with non-achieving MMR within 12 months (p = 0.0388, odds ratio 1.479, 95%CI: 1.020 to 2.143). Thus, 10% of the tested non-responders (cut-off ≥ 5.9) could have been predicted already at the time of diagnosis. Future scoring of ESPL1, PTTG1 and PTTG1IP transcript levels may be a helpful tool in risk stratification of CML patients before initiation of TKI first = line treatment.

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Patients with chronic myeloid leukaemia in chronic phase (CML-CP) who have a sustained deep molecular response (DMR) are eligible to discontinue treatment and attempt treatment-free remission (TFR). In the DASFREE study (ClinicalTrials.gov; NCT01850004), the 2-year TFR rate after dasatinib discontinuation was 46%; here we present the 5-year update. Patients with a stable DMR after ≥2 years of dasatinib therapy discontinued treatment and were followed for 5 years. At a minimum follow-up of 60 months, in 84 patients discontinuing dasatinib, the 5-year TFR rate was 44% (n = 37). No relapses occurred after month 39 and all evaluable patients who relapsed and restarted dasatinib (n = 46) regained a major molecular response in a median of 1.9 months. The most common adverse event during the off-treatment period was arthralgia (18%, 15/84); a total of 15 withdrawal events were reported in nine patients (11%). At the 5-year final follow-up, almost half of the patients who discontinued dasatinib after a sustained DMR maintained TFR. All evaluable patients who experienced a relapse quickly regained a DMR after restarting dasatinib, demonstrating that dasatinib discontinuation is a viable and potentially long-term option in patients with CML-CP. The safety profile is consistent with the previous report.

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Asciminib, a first-in-class, allosteric inhibitor of BCR-ABL1 that acts by STAMP (Specifically Targeting the ABL Myristoyl Pocket), is a novel therapeutic option for patients with chronic myeloid leukemia (CML). In the global, phase 3, open-label ASCEMBL study in patients with CML in chronic phase (CML-CP) pretreated with ≥2 tyrosine kinase inhibitors (TKIs) (NCT03106779), asciminib (40 mg twice-daily) demonstrated significant superiority over the ATP-competitive TKI bosutinib (500 mg once daily) for the primary endpoint of major molecular response (MMR; BCR::ABL1 transcript levels on the international scale [BCR::ABL1IS ] ≤0.1%) at week 24. Here, we report results from a descriptive subgroup analysis of Japanese patients enrolled in ASCEMBL study (data cut-off: May 25, 2020). Overall, 16 Japanese patients were randomized (asciminib, n = 13; bosutinib, n = 3). At week 24, the MMR rate with asciminib was 30.8% (4/13; 95% confidence interval [CI], 9.09-61.43). BCR::ABL1IS ≤1% and complete cytogenic response (CCyR) at week 24 were 61.5% (8/13 patients) and 50.0% (4/8 patients), respectively. In the bosutinib group, no patient achieved MMR, CCyR, or BCR::ABL1IS ≤1%, but results were limited by the low number of patients. The safety profile of asciminib was comparable to that previously observed in the overall study population. Findings from this Japanese subgroup analysis of the ASCEMBL study support the use of asciminib for the treatment of Japanese patients with CML-CP previously treated with ≥2 TKIs. ClinicalTrials.gov Identifier: NCT03106779.

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Imatinib is the most common first-line tyrosine kinase inhibitor (TKI) used to treat chronic-phase chronic myeloid leukemia (CP-CML). However, only a proportion of patients achieve major molecular response (MMR), so there is a need to find biological factors that aid the selection of the optimal therapeutic strategy (imatinib vs. more potent second-generation TKIs). The aim of this retrospective study was to understand the contribution of germline single-nucleotide variants (gSNVs) in the achievement of MMR with imatinib. In particular, a discovery cohort including 45 CP-CML patients was analyzed through the DMET array, which interrogates 1936 variants in 231 genes related to the absorption, distribution, metabolism and excretion (ADME) process. Variants statistically significant in the discovery cohort were then tested in an extended and independent cohort of 137 CP-CML patients. Finally, a total of 7 gSNVs (ABCG1-rs492338, ABCB11-rs496550, ABCB11-rs497692, CYP2D6-rs1135840, CYP11B1-rs7003319, MAT1A-rs4934027 and SLC22A1-rs628031) and one haplotype in the ABCB11 gene were significantly associated with the achievement of MMR with first-line imatinibtreatment. In conclusion, we identified a genetic signature of response to imatinib in CP-CML patients that could be useful in selecting those patients that may benefit from starting imatinib as first-line therapy, therefore avoiding the toxicity related to second-generation TKIs.

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PURPOSE: We evaluated the plasma exposure and response relationships of nilotinib for patients with newly diagnosed chronic myeloid leukemia (CML) in real-world practice. METHODS: For the 26 patients enrolled in this study, at 3, 6, 12, and 24 months after nilotinib administration, the trough plasma concentrations (Ctrough) of nilotinib were analyzed. The relationships between nilotinib Ctrough and the molecular response to nilotinib treatment at each point (each n = 26) were evaluated. RESULTS: Median nilotinib Ctrough values were significantly higher in patients with a major molecular response (MMR) at 3 months than in patients without an MMR (809 and 420 ng/mL, respectively; P = 0.046). Based on the area under the receiver-operating characteristic curve, the threshold value of the nilotinib Ctrough at 3 months for predicting MMR achievement was 619 ng/mL at the best sensitivity (71.4%) and specificity (77.8%). Patients with a nilotinib Ctrough of above 619 ng/mL had a significantly shorter time to achievement of a deep molecular response (DMR; 9.0 and 18.0 months, respectively; P = 0.020) and higher rates of DMR by 2 years in Kaplan-Meier plots (P = 0.025) compared with that in patients with a nilotinib Ctrough of less than 619 ng/mL. CONCLUSION: For patients with newly diagnosed CML, the nilotinib dose may be adjusted using a Ctrough of above 619 ng/mL as the minimum effective concentration, i.e., the lowest concentration required for MMR or DMR achievement within a shorter time, during early stages after beginning therapy to obtain faster and deeper clinical responses.

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The discovery of the tyrosine kinase inhibitor (TKI) imatinib in the early 2000's revolutionized the treatment and prognosis of patients with chronic myeloid leukemia (CML) [Hochhaus et al. in N Engl J Med 376:917-927, 2017]. The treatment of patients with CML has changed dramatically since the approval of imatinib and other TKIs. Before the TKI era, newly diagnosed patients would undergo HLA typing to try to identify a well-matched donor, and then proceed quickly to allogeneic hematopoietic cell transplantation (HCT). With the introduction of imatinib followed a few years later by dasatinib, nilotinib, then bosutinib, treatment approaches changed in a dramatic way. Transplantation is no longer an upfront treatment option for newly diagnosed CML patients, and in fact, it is very rarely used in the management of a patient with CML currently. The management of CML patients has been a model of personalized medicine or targeted therapy that is being emulated in the treatment of many other hematologic malignancies and solid tumors such as lung cancer [Soverini et al. in Mol Cancer 17:49, 2018]. The Philadelphia Chromosome (Ph) which leads to the formation of the BCR-ABL fusion gene and its product the BCR-ABL protein is the cause of CML. With effective targeting of this protein with the available TKIs, the disease is completely controllable if not curable for most patients. Life expectancy for patients with CML is essentially normal. Quality of life becomes an important goal including the potential for pregnancy, and ultimately the chance to discontinue all TKI therapy permanently. The three cases outlined below serve to highlight some of the important issues in the management of patients with CML in the post-TKI era.

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Myeloid-derived suppressor cells (MDSCs) represent phenotypically heterogeneous populations that suppress tumor-specific T-cell responses. MDSCs are produced from myeloid precursors in emergent states and are increased in several hematologic malignancies. We evaluated the differences in the levels and prognostic significance of MDSCs according to the clinical status of chronic myeloid leukemia (CML). The percentages and numbers of granulocytic (g)MDSCs and monocytic (m)MDSCs in peripheral blood (PB) and bone marrow (BM) aspirates were determined by five-color flow cytometry (HLA-DR/CD11b/CD15/CD33/CD14). The median BM-gMDSC% and PB-gMDSC% of the CML group were lower than those of the complete hematologic response (CHR) and control groups (P<0.001). In the CHR group, patients with major molecular response (MMR) showed higher median BM-gMDSC% than those without MMR (P=0.039). Conversely, the PB-mMDSC number of the CML group was higher than those of the CHR and control groups (P<0.001). Patients with high PB-gMDSC number exhibited superior survival to those with low PB-gMDSC number (P=0.021), and patients with high PB-mMDSC% showed inferior survival to those with low PB-mMDSC%, but there was no statistical significance (P=0.182). Increased gMDSCs at CHR may reflect non-leukemic granulopoiesis, and a high number of PB-gMDSCs suggests better prognosis in CML. However, mMDSCs may be associated with malignant conditions and poor prognosis.

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Treatment of chronic myeloid leukemia (CML) has evolved dramatically in recent years. In this regard, the introduction of second-generation tyrosine kinase inhibitors (TKI) has revolutionized therapeutic goals, and it is now desirable to obtain treatment-free remission (TFR), i.e. when a patient who has stopped TKI therapy maintains a major molecular response and does not need to restart treatment. This report summarizes the main findings from a group of expert hematologists in Italy who met to discuss treatment and management of patients with CML with focus on broad-ranging aspects of TFR. A survey was used to obtain information about the clinicians' experience with TFR and to better understand the clinical and psychological issues that patients and physicians face when considering TFR. The overall goal was to explore the possibility of discontinuing treatment from multiple points of view, considering both clinical aspects of TFR as well as psychological management of patients. Practical information is provided on aspects associated with initiating TFR, clinical data supporting it, the role of monitoring, and management of discontinuation-related adverse events. This publication outlines many of the shortcomings and highlights proposed solutions for routine clinical practice, and provides an overview of the literature relative to TFR.

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INTRODUCTION: Glutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to tyrosine kinase inhibitors in chronic myeloid leukemia (CML). We aimed to analyze relation of different GST gene sequence variants with susceptibility and response to Imatinib in CML. MATERIAL AND METHODS: A total of 150 CML cases and equal number of age and gender matched healthy controls were genotyped for five GST polymorphisms by multiplex-PCR and PCR-RFLP techniques. BCR-ABL1 transcripts were quantified by quantitative Real Time PCR (qRT-PCR). RESULTS: GSTT1, GSTO1, and GSTO2 SNPs revealed no association, while as GSTM1null genotype was observed to protect against the development of CML (OR = 0.53, P = .01). GSTP1 variant genotypes AG (OR = 2.1, P = .003) and GG (OR = 5.6, P < .001), significantly associated with increased risk of CML. Combined genotype analysis showed protective impact of GSTT1present /GSTM1null (OR = 0.44, P = .003) while as GSTT1present /GSTP1-GG (OR = 6.92, P < .001) and GSTM1present /GSTP1-GG (OR = 6.33, P < .001), significantly increased CML risk. GSTM1null genotype individually and in combination with GSTT1present associated with superior rate of major molecular response (MMR) and event free survival (EFS) (log-rank P = .029). GSTO2-AG+GG genotype associated with significantly inferior MMR rates at 3, 6, and 12 months. Also, patients with GSTO2-GG genotype showed significantly reduced EFS (log-rank P = .025). Multivariate analysis confirmed GSTM1null as a better (HR:0.19, P = .029) and GSTO2-GG genotype as an independent poor prognostic factor (HR:2.29, P = .037). CONCLUSION: GSTM1null genotype seems to have a better prognostic role while GSTP1 variants significantly increase CML risk. Also, results support a correlation between disease outcome and GSTO2 polymorphism.

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Context Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Aims We aim to evaluate the responses and safety of upfront Nilotinib therapy in Indian CML patients. Setting and Design We retrospectively reviewed the medical records of CML patients who received Nilotinib as an upfront treatment at our center between January 1, 2011 and October 15, 2019.The follow-up was taken till March 31, 2020. Results Forty One patients ( n = 36 chronic phase and five accelerated-phase CML) received frontline Nilotinib. Median age was 39 years (21-63) with male-to-female ratio of 1.1: 1. At 3 months, 96.9% patients achieved BCR-ABL of ≤10% at international scale. By the end of 12 months, 71.5% patients achieved major molecular response (BCR-ABL ≤0.1%) and 91.4% patients achieved complete cytogenetic response assessed by BCR-ABL polymerase chain reaction of ≤1%. Common toxicities observed were weight gain, thrombocytopenia, corrected QT prolongation, and elevated serum amylase in 14 (34.1%), 7(17.07%), 4(9.7%), and 4(9.7%) patients, respectively. Overall, five patients had loss of response with further progression and death in three patients. At a median of 43.7 months, 38 patients survived with estimated 3 year event-free survival and overall survival of 65 ± 9 and 93 ± 5%. Conclusion This study showed remarkable good response with upfront Nilotinib in Indian patients with CML.

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Therapy with tyrosine kinase inhibitors (TKI) allows to achieve a deep molecular response in 6070% of patients with chronic myeloid leukemia (CML). According to the current guidelines CML patients receive a long-term treatment with TKI in standard dose. The frequently observed adverse effects (AE) of TKI therapy are mostly dose-dependent. A new treatment approach with TKI use in reduced dose is desirable for the CML patients with existing AE or with a high risk of AE occurrence. We report the two cases of successful long-term treatment of CML patients with reduced doses of second generation TKIs. The aim of the TKI dose reduction was to reduce the clinical manifestations of drug toxicities and to prevent the AE.

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Chronic myelogenous leukemia (CML) is a hematopoietic disorder caused by the BCR/ABL gene or Philadelphia chromosome. The first Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treatment of CML was imatinib in 2001. Since then, multiple therapies, such as nilotinib, dasatinib, bosutinib, and, more recently, ponatinib, have made their way as viable treatment options for first-line and secondary therapies. Most patients tend to respond to first-line treatment. Although there is a subset of patients who do not achieve complete molecular response with first line, newer options have proven beneficial. As we progress through therapies, there still remain some patients who do not adequately respond to current available therapies. The treatment options and guidelines become more difficult in such situations, not only with respect to cost but also patient quality of life and satisfaction. We discuss a 75-year-old white female with CML, who has had multiple therapies with hematological remission but has never achieved complete molecular remission, currently on bosutinib and tolerating it well.

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The median age of diagnosis for chronic myeloid leukemia (CML) in India is 35 years on the contrary to western literature which is 47 years. The outcome of the elderly patient in CML TKI era is not reported from the Indian population. However, Western literature suggests that use of TKI alleviate the adverse impact of age in outcomes of CML. This study was carried out to analyze the clinical profile and outcome of elderly, in comparison with younger patients with CML. We retrospectively analyzed CML patients treated at our department from January 2008 to December 2017. The data cutoff date was December 2018. The cohorts of 712 patients were divided into two groups. Patients belonging to the age group of ≥ 60 years were classified as the study group and those who were 18-60 years were used as controls. Patient's clinical history, examination and milestones in terms of achieving hematological, molecular responses and toxicity profile were also recorded. The total of 712 patients, 52 patients in the study group and 660 patients in the control group were treated during the study period. The study group was having more co-morbidities than the control group (15.3% vs. 4.5%). Patients having high-risk EUTOS score were similar in both groups (38.4% vs. 37.6%). The patients presented in blast phase were higher in the study group as compared to control group (9.6% vs. 6.36%) but the differences were not statistically significant. Rates of achieving a hematological response at 3 months (85.1% vs. 86.89%) and the major molecular response at 18 months (54.3% vs. 60.16%) were almost similar in both groups. However, hematological toxicity, muscle cramps and gastritis were reported more in elderly patients. The outcome of CML patients in TKI era do not differ in elderly patients. However, toxicity profile was not significantly inferior in elderly patients.

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BACKGROUND: In a developing country like Yemen, data are limited regarding the outcome of imatinib treatment of chronic myeloid leukemia and the effect of nonadherence to imatinib treatment and previous duration of hydroxyurea treatment. PATIENTS AND METHODS: A longitudinal cohort study, which included 164 Yemeni patients, was performed. Data regarding the disease characteristics, adherence to treatment (the medication possession ratio) and outcome were analyzed. RESULTS: After a median follow-up of 60 months and a median duration of imatinib treatment of 46 months, 79 (48.2%) patients were adherent to treatment. In adherent patients, the overall survival and progression-free survival (PFS) were 78 (98.7%) and 73 patients (92.4%), respectively and major molecular response (MMR) rates at 12 months and at 46 months were 32 (41.0%) and 45 patients (57.0%), respectively, compared with 67 (78.8%), 51 (60%), 5 (6.9%), and 2 patients (2.4%), respectively, in nonadherent patients (P < .001 for all parameters). Nonadherence to imatinib treatment and duration of hydroxyurea treatment of more than 12 months before starting imatinib were found to adversely affect PFS in univariate (hazard ratio [HR], 7.5 and 9.7, respectively and P < .001 for both) and multivariate (HR, 5.6 and 9.3; P = .001 and P < .001, respectively) analysis. High risk Sokal score was found to adversely affect PFS in univariate analysis (HR of high to low risk, 2.8; P < .022) but not in multivariate analysis. CONCLUSION: Yemeni patients who were adherent to imatinib therapy achieved response rates similar to that of international standards. Nonadherence to imatinib treatment and previous duration of hydroxyurea treatment for more than 12 months, as a proxy of long interval between diagnosis and starting imatinib treatment, reduced the optimal response to imatinib therapy.

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Treatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase (CML-CP) is considered a feasible option, especially with the ability of second-generation tyrosine kinase inhibitors to induce higher rates of sustained deep molecular response (DMR). DASFREE is an open-label, single-arm, multicenter phase II trial assessing TFR after dasatinib discontinuation in patients with CML-CP (N = 84). At 2 years, TFR was 46% in all patients. Multivariate analyses revealed statistically significant associations between 2-year TFR and duration of prior dasatinib (≥median; p = .0051), line of therapy (first line; p = .0138), and age (>65 years; p = .0012). No disease transformation occurred, and the most common adverse events experienced off treatment were musculoskeletal (observed in 30 patients); however, dasatinib withdrawal events were reported in nine patients (11%) by the investigator. Overall, these findings support the feasibility of discontinuing dasatinib for patients with CML-CP in sustained DMR in the first line and beyond.

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BACKGROUND: Imatinib mesylate has revolutionized the treatment of patients with chronic myeloid leukaemia (CML); however, some patients fail to respond and have a poor prognosis. Evaluation of molecular response to imatinib is a sensitive method can help physicians make better and quicker therapeutic decisions in the course of this disease. This study aims to evaluate the molecular response to generic imatinib in Iranian patients with CML. PATIENTS AND METHODS: This prospective study consisted of 255 newly diagnosed patients with CML who received imatinib. Molecular response was analyzed at 3 and 6 months from the start of the treatment and then every 6 months, and long-term outcomes, including overall survival (OS) and progression-free survival (PFS), were evaluated. RESULTS: At a median follow-up of 34.8 months (range, 3-84 months, (the OS and PFS at 7 years were 94.3% and 92.9%, respectively. Eighty-four-month PFS rates in patients with a BCR-ABLIS ≤ 10% at 3 months and BCR-ABLIS ≤ 1% at 6 months were significantly higher than patients who did not obtain these levels of BCR-ABL transcripts (P = .004 and P < .0001, respectively). The proportion of patients who achieved major molecular response (MMR) was 44.1%, 52.97%, and 60.75% at 12, 18, and 24 months, respectively. At 12, 18, and 84 months, the PFS rates in patients who achieved MMR were significantly higher than in patients who did not achieve MMR (P = .002, P < .0001, and P = .003, respectively). CONCLUSIONS: The data of this prospective study are highly comparable with that from clinical trials and prospective international studies.

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