CML

Key clinical point: Nilotinib treatment for chronic myeloid leukemia (CML) may be associated with arterial complications, particularly involving the carotid artery. These results urge for cardiovascular evaluation, with close vascular follow-up, in all patients initiating nilotinib.

Major finding: Arterial ultrasound anomalies were present in 25 patients, with the carotid bulb being the most involved territory (44%). Overall, vascular arterial anomaly was present in 33.8% of patients. Vascular adverse events were also present in 12.5% of patients with no cardiovascular risk factors.

Study details: This retrospective study evaluated 74 patients with CML treated with nilotinib at the Paoli-Calmettes Institute, Marseille, between 2006 and 2015.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Sarlon-Bartoli G et al. J Med Vasc. 2021 Mar 6. doi: 10.1016/j.jdmv.2021.02.002.

Key clinical point: Nilotinib treatment for chronic myeloid leukemia (CML) may be associated with arterial complications, particularly involving the carotid artery. These results urge for cardiovascular evaluation, with close vascular follow-up, in all patients initiating nilotinib.

Major finding: Arterial ultrasound anomalies were present in 25 patients, with the carotid bulb being the most involved territory (44%). Overall, vascular arterial anomaly was present in 33.8% of patients. Vascular adverse events were also present in 12.5% of patients with no cardiovascular risk factors.

Study details: This retrospective study evaluated 74 patients with CML treated with nilotinib at the Paoli-Calmettes Institute, Marseille, between 2006 and 2015.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Sarlon-Bartoli G et al. J Med Vasc. 2021 Mar 6. doi: 10.1016/j.jdmv.2021.02.002.

Key clinical point: Nilotinib treatment for chronic myeloid leukemia (CML) may be associated with arterial complications, particularly involving the carotid artery. These results urge for cardiovascular evaluation, with close vascular follow-up, in all patients initiating nilotinib.

Major finding: Arterial ultrasound anomalies were present in 25 patients, with the carotid bulb being the most involved territory (44%). Overall, vascular arterial anomaly was present in 33.8% of patients. Vascular adverse events were also present in 12.5% of patients with no cardiovascular risk factors.

Study details: This retrospective study evaluated 74 patients with CML treated with nilotinib at the Paoli-Calmettes Institute, Marseille, between 2006 and 2015.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Sarlon-Bartoli G et al. J Med Vasc. 2021 Mar 6. doi: 10.1016/j.jdmv.2021.02.002.

Key clinical point: With broader use of novel tyrosine kinase inhibitor (TKI) and a better understanding of the disease, the relative survival (RS) of patients with chronic myeloid leukemia (CML) in the United States has improved but is still not on par with the general population.

Major finding: Overall, rates of 5- and 10-year RS were 83.4% (95% confidence interval [CI], 81.6%-85.0%) and 72.8% (95% CI, 69.7%-75.6%), respectively. Ten-year RS was worse among patients aged 65 years or older vs. those aged less than 65 years. The 5-year RS for patients diagnosed between 2008-2014 and 2001-2007 was 87.0% and 81.0%, respectively (P less than .001).

Study details: Findings are from a US population-based study, including 3,946 patients diagnosed with BCR-ABL–positive CML during the period between the introduction of TKIs and the last available follow-up data (2001-2014).

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jamy O et al. Am J Hematol. 2021 Apr 17. doi: 10.1002/ajh.26195.

Key clinical point: With broader use of novel tyrosine kinase inhibitor (TKI) and a better understanding of the disease, the relative survival (RS) of patients with chronic myeloid leukemia (CML) in the United States has improved but is still not on par with the general population.

Major finding: Overall, rates of 5- and 10-year RS were 83.4% (95% confidence interval [CI], 81.6%-85.0%) and 72.8% (95% CI, 69.7%-75.6%), respectively. Ten-year RS was worse among patients aged 65 years or older vs. those aged less than 65 years. The 5-year RS for patients diagnosed between 2008-2014 and 2001-2007 was 87.0% and 81.0%, respectively (P less than .001).

Study details: Findings are from a US population-based study, including 3,946 patients diagnosed with BCR-ABL–positive CML during the period between the introduction of TKIs and the last available follow-up data (2001-2014).

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jamy O et al. Am J Hematol. 2021 Apr 17. doi: 10.1002/ajh.26195.

Key clinical point: With broader use of novel tyrosine kinase inhibitor (TKI) and a better understanding of the disease, the relative survival (RS) of patients with chronic myeloid leukemia (CML) in the United States has improved but is still not on par with the general population.

Major finding: Overall, rates of 5- and 10-year RS were 83.4% (95% confidence interval [CI], 81.6%-85.0%) and 72.8% (95% CI, 69.7%-75.6%), respectively. Ten-year RS was worse among patients aged 65 years or older vs. those aged less than 65 years. The 5-year RS for patients diagnosed between 2008-2014 and 2001-2007 was 87.0% and 81.0%, respectively (P less than .001).

Study details: Findings are from a US population-based study, including 3,946 patients diagnosed with BCR-ABL–positive CML during the period between the introduction of TKIs and the last available follow-up data (2001-2014).

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jamy O et al. Am J Hematol. 2021 Apr 17. doi: 10.1002/ajh.26195.

Key clinical point: Gastrointestinal adverse event (AE) profiles differed significantly among different tyrosine kinase inhibitors (TKIs) and should be considered for optimal therapy selection for patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The mean incidence of all gastrointestinal AEs was highest with bosutinib (52.9%), followed by imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). The incidence of most gastrointestinal AEs was consistently and significantly higher for bosutinib and lower for nilotinib vs. other TKIs (P less than .0016). Overall survival rates over 12 months were more than 90% for all TKIs.

Study details: Meta-analysis of 43 peer-reviewed studies including a heterogeneous population of 10,789 patients with CML with varying disease stages.

Disclosures: This study was funded by Georgia Institute of Technology President’s Undergraduate Research Award, a grant from Incyte pharmaceuticals, Children’s Hospital of Atlanta Aflac pilot grant, and National Science Foundation CAREER award. V Kota reported honoraria for consultancy from Novartis and Pfizer. Other authors declared no conflicts of interest.

Source: Mohanavelu P et al. Cancers. 2021 Apr 1. doi: 10.3390/cancers13071643.

Key clinical point: Gastrointestinal adverse event (AE) profiles differed significantly among different tyrosine kinase inhibitors (TKIs) and should be considered for optimal therapy selection for patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The mean incidence of all gastrointestinal AEs was highest with bosutinib (52.9%), followed by imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). The incidence of most gastrointestinal AEs was consistently and significantly higher for bosutinib and lower for nilotinib vs. other TKIs (P less than .0016). Overall survival rates over 12 months were more than 90% for all TKIs.

Study details: Meta-analysis of 43 peer-reviewed studies including a heterogeneous population of 10,789 patients with CML with varying disease stages.

Disclosures: This study was funded by Georgia Institute of Technology President’s Undergraduate Research Award, a grant from Incyte pharmaceuticals, Children’s Hospital of Atlanta Aflac pilot grant, and National Science Foundation CAREER award. V Kota reported honoraria for consultancy from Novartis and Pfizer. Other authors declared no conflicts of interest.

Source: Mohanavelu P et al. Cancers. 2021 Apr 1. doi: 10.3390/cancers13071643.

Key clinical point: Gastrointestinal adverse event (AE) profiles differed significantly among different tyrosine kinase inhibitors (TKIs) and should be considered for optimal therapy selection for patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The mean incidence of all gastrointestinal AEs was highest with bosutinib (52.9%), followed by imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). The incidence of most gastrointestinal AEs was consistently and significantly higher for bosutinib and lower for nilotinib vs. other TKIs (P less than .0016). Overall survival rates over 12 months were more than 90% for all TKIs.

Study details: Meta-analysis of 43 peer-reviewed studies including a heterogeneous population of 10,789 patients with CML with varying disease stages.

Disclosures: This study was funded by Georgia Institute of Technology President’s Undergraduate Research Award, a grant from Incyte pharmaceuticals, Children’s Hospital of Atlanta Aflac pilot grant, and National Science Foundation CAREER award. V Kota reported honoraria for consultancy from Novartis and Pfizer. Other authors declared no conflicts of interest.

Source: Mohanavelu P et al. Cancers. 2021 Apr 1. doi: 10.3390/cancers13071643.

Key clinical point: Bosutinib demonstrated comparable efficacy to nilotinib and dasatinib for first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Besides bosutinib demonstrating better deep molecular responses, MR4 vs. nilotinib (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.38-0.84) and MR4.5 vs. dasatinib (OR, 0.56; 95% CI, 0.35-0.90) at 24 months, other parameters like major molecular response, complete cytogenetic response, and disease progression by 24 months were similar with bosutinib vs. nilotinib and dasatinib.

Study details: Unanchored matching-adjusted indirect treatment comparisons were performed using data from bosutinib (BFORE), nilotinib (ENESTnd), and dasatinib (DASISION) trials.

Disclosures: This study was sponsored by Pfizer. The authors including the lead author reported being an employee and/or share or equity holders of Ingress-health BV, which received financial assistance from Pfizer for the conduct of the study.

Source: Muresan B et al. Curr Med Res Opin. 2021 Apr 2. doi: 10.1080/03007995.2021.1896489.

Key clinical point: Bosutinib demonstrated comparable efficacy to nilotinib and dasatinib for first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Besides bosutinib demonstrating better deep molecular responses, MR4 vs. nilotinib (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.38-0.84) and MR4.5 vs. dasatinib (OR, 0.56; 95% CI, 0.35-0.90) at 24 months, other parameters like major molecular response, complete cytogenetic response, and disease progression by 24 months were similar with bosutinib vs. nilotinib and dasatinib.

Study details: Unanchored matching-adjusted indirect treatment comparisons were performed using data from bosutinib (BFORE), nilotinib (ENESTnd), and dasatinib (DASISION) trials.

Disclosures: This study was sponsored by Pfizer. The authors including the lead author reported being an employee and/or share or equity holders of Ingress-health BV, which received financial assistance from Pfizer for the conduct of the study.

Source: Muresan B et al. Curr Med Res Opin. 2021 Apr 2. doi: 10.1080/03007995.2021.1896489.

Key clinical point: Bosutinib demonstrated comparable efficacy to nilotinib and dasatinib for first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Besides bosutinib demonstrating better deep molecular responses, MR4 vs. nilotinib (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.38-0.84) and MR4.5 vs. dasatinib (OR, 0.56; 95% CI, 0.35-0.90) at 24 months, other parameters like major molecular response, complete cytogenetic response, and disease progression by 24 months were similar with bosutinib vs. nilotinib and dasatinib.

Study details: Unanchored matching-adjusted indirect treatment comparisons were performed using data from bosutinib (BFORE), nilotinib (ENESTnd), and dasatinib (DASISION) trials.

Disclosures: This study was sponsored by Pfizer. The authors including the lead author reported being an employee and/or share or equity holders of Ingress-health BV, which received financial assistance from Pfizer for the conduct of the study.

Source: Muresan B et al. Curr Med Res Opin. 2021 Apr 2. doi: 10.1080/03007995.2021.1896489.

Key clinical point: Leukemic stem cells (LSCs) persisted in bone marrow (BM) but not in peripheral blood (PB) of patients with chronic-phase chronic myeloid leukemia (CML-CP) with deep molecular response (DMR). Investigating BM LSCs before deciding tyrosine kinase inhibitor (TKI) discontinuation could help achieve and maintain stable treatment-free remission (TFR).

Major finding: LSCs persisted in BM of patients in DMR (281.1 LSC/10⁶ white blood cells [WBCs]) but not in PB. BM LSCs were observed in newly diagnosed patients (805 LSCs/10⁶ WBC) and TKI-treated patients with BCR-ABL-positive hematopoiesis (143.5 LSCs/10⁶ WBC). PB LSCs were highest in newly diagnosed patients (237.5 LSCs/μL) but reduced in TKI-treated patients with BCR-ABL-positive hematopoiesis (13.5 LSCs/μL).

Study details: This study included 38 patients with CML-CP who were either recently diagnosed (n=7), had BCR-ABL-positive hematopoiesis under TKI therapy (n=19), or achieved DMR with TKIs (n=12).

Disclosures: This study was funded by Pfizer through Pfizer Independent Medical Grants program. The authors declared no conflicts of interest.

Source: Ilhan O et al. Int J Lab Haematol. 2021 Apr 9. doi: 10.1111/ijlh.13528.

Key clinical point: Leukemic stem cells (LSCs) persisted in bone marrow (BM) but not in peripheral blood (PB) of patients with chronic-phase chronic myeloid leukemia (CML-CP) with deep molecular response (DMR). Investigating BM LSCs before deciding tyrosine kinase inhibitor (TKI) discontinuation could help achieve and maintain stable treatment-free remission (TFR).

Major finding: LSCs persisted in BM of patients in DMR (281.1 LSC/10⁶ white blood cells [WBCs]) but not in PB. BM LSCs were observed in newly diagnosed patients (805 LSCs/10⁶ WBC) and TKI-treated patients with BCR-ABL-positive hematopoiesis (143.5 LSCs/10⁶ WBC). PB LSCs were highest in newly diagnosed patients (237.5 LSCs/μL) but reduced in TKI-treated patients with BCR-ABL-positive hematopoiesis (13.5 LSCs/μL).

Study details: This study included 38 patients with CML-CP who were either recently diagnosed (n=7), had BCR-ABL-positive hematopoiesis under TKI therapy (n=19), or achieved DMR with TKIs (n=12).

Disclosures: This study was funded by Pfizer through Pfizer Independent Medical Grants program. The authors declared no conflicts of interest.

Source: Ilhan O et al. Int J Lab Haematol. 2021 Apr 9. doi: 10.1111/ijlh.13528.

Key clinical point: Leukemic stem cells (LSCs) persisted in bone marrow (BM) but not in peripheral blood (PB) of patients with chronic-phase chronic myeloid leukemia (CML-CP) with deep molecular response (DMR). Investigating BM LSCs before deciding tyrosine kinase inhibitor (TKI) discontinuation could help achieve and maintain stable treatment-free remission (TFR).

Major finding: LSCs persisted in BM of patients in DMR (281.1 LSC/10⁶ white blood cells [WBCs]) but not in PB. BM LSCs were observed in newly diagnosed patients (805 LSCs/10⁶ WBC) and TKI-treated patients with BCR-ABL-positive hematopoiesis (143.5 LSCs/10⁶ WBC). PB LSCs were highest in newly diagnosed patients (237.5 LSCs/μL) but reduced in TKI-treated patients with BCR-ABL-positive hematopoiesis (13.5 LSCs/μL).

Study details: This study included 38 patients with CML-CP who were either recently diagnosed (n=7), had BCR-ABL-positive hematopoiesis under TKI therapy (n=19), or achieved DMR with TKIs (n=12).

Disclosures: This study was funded by Pfizer through Pfizer Independent Medical Grants program. The authors declared no conflicts of interest.

Source: Ilhan O et al. Int J Lab Haematol. 2021 Apr 9. doi: 10.1111/ijlh.13528.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) is common in routine clinical practice and is as successful as when performed within a clinical trial.

Major finding: TKI discontinuation of longer than 1 month was reported in 235 patients. Overall, 128 patients discontinued as they achieved a deep molecular response, of which 70.3% discontinued outside a clinical trial. Among patients discontinuing TKI outside a clinical trial, 62.2% remained treatment free after a median follow-up of 1.6 years, which compares favorably to that observed in clinical trials.

Study details: This was a retrospective, population-based study of 584 patients diagnosed with CML-CP between 2007 and 2012 from the Swedish CML registry.

Disclosures: No funding source was identified. U Olsson-Stromberg reported honoraria from Ariad. The other authors had no disclosures.

Source: Flygt H et al. Br J Haematol. 2021 Mar 30. doi: 10.1111/bjh.17392.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) is common in routine clinical practice and is as successful as when performed within a clinical trial.

Major finding: TKI discontinuation of longer than 1 month was reported in 235 patients. Overall, 128 patients discontinued as they achieved a deep molecular response, of which 70.3% discontinued outside a clinical trial. Among patients discontinuing TKI outside a clinical trial, 62.2% remained treatment free after a median follow-up of 1.6 years, which compares favorably to that observed in clinical trials.

Study details: This was a retrospective, population-based study of 584 patients diagnosed with CML-CP between 2007 and 2012 from the Swedish CML registry.

Disclosures: No funding source was identified. U Olsson-Stromberg reported honoraria from Ariad. The other authors had no disclosures.

Source: Flygt H et al. Br J Haematol. 2021 Mar 30. doi: 10.1111/bjh.17392.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) is common in routine clinical practice and is as successful as when performed within a clinical trial.

Major finding: TKI discontinuation of longer than 1 month was reported in 235 patients. Overall, 128 patients discontinued as they achieved a deep molecular response, of which 70.3% discontinued outside a clinical trial. Among patients discontinuing TKI outside a clinical trial, 62.2% remained treatment free after a median follow-up of 1.6 years, which compares favorably to that observed in clinical trials.

Study details: This was a retrospective, population-based study of 584 patients diagnosed with CML-CP between 2007 and 2012 from the Swedish CML registry.

Disclosures: No funding source was identified. U Olsson-Stromberg reported honoraria from Ariad. The other authors had no disclosures.

Source: Flygt H et al. Br J Haematol. 2021 Mar 30. doi: 10.1111/bjh.17392.

Key clinical point: Upfront imatinib treatment was equally effective in elderly vs. younger patients with chronic myeloid leukemia (CML). Management of therapy-related adverse events (AEs) may lead to better clinical outcomes.

Major finding: Although overall survival was higher in younger patients (P less than .001), rates of early molecular response (MR), complete cytogenic response, major MR, deep MR, and event-free survival were not significantly different between elderly and younger patients. Hematological AEs (24% vs. 7%; P = .005) and AE-related dose reduction (33% vs. 9%; P less than .001) were higher in elderly vs. younger patients.

Study details: Data come from a retrospective study of 158 elderly (aged 60 years or older, n=33) and younger (aged less than 60 years, n=125) patients with Philadelphia-positive CML.

Disclosures: No funding source was identified. The lead author, AE Eşkazan and T Soysal reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Eşkazan AE et al. Clin Lymph Myel Leuk. 2021 Apr 13. doi: 10.1016/j.clml.2021.04.005.

Key clinical point: Upfront imatinib treatment was equally effective in elderly vs. younger patients with chronic myeloid leukemia (CML). Management of therapy-related adverse events (AEs) may lead to better clinical outcomes.

Major finding: Although overall survival was higher in younger patients (P less than .001), rates of early molecular response (MR), complete cytogenic response, major MR, deep MR, and event-free survival were not significantly different between elderly and younger patients. Hematological AEs (24% vs. 7%; P = .005) and AE-related dose reduction (33% vs. 9%; P less than .001) were higher in elderly vs. younger patients.

Study details: Data come from a retrospective study of 158 elderly (aged 60 years or older, n=33) and younger (aged less than 60 years, n=125) patients with Philadelphia-positive CML.

Disclosures: No funding source was identified. The lead author, AE Eşkazan and T Soysal reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Eşkazan AE et al. Clin Lymph Myel Leuk. 2021 Apr 13. doi: 10.1016/j.clml.2021.04.005.

Key clinical point: Upfront imatinib treatment was equally effective in elderly vs. younger patients with chronic myeloid leukemia (CML). Management of therapy-related adverse events (AEs) may lead to better clinical outcomes.

Major finding: Although overall survival was higher in younger patients (P less than .001), rates of early molecular response (MR), complete cytogenic response, major MR, deep MR, and event-free survival were not significantly different between elderly and younger patients. Hematological AEs (24% vs. 7%; P = .005) and AE-related dose reduction (33% vs. 9%; P less than .001) were higher in elderly vs. younger patients.

Study details: Data come from a retrospective study of 158 elderly (aged 60 years or older, n=33) and younger (aged less than 60 years, n=125) patients with Philadelphia-positive CML.

Disclosures: No funding source was identified. The lead author, AE Eşkazan and T Soysal reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Eşkazan AE et al. Clin Lymph Myel Leuk. 2021 Apr 13. doi: 10.1016/j.clml.2021.04.005.

Key clinical point: Bosutinib was more effective than imatinib as first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) with manageable toxicity, particularly in the Asian subpopulation of BFORE trial.

Major finding: Rates of major molecular response favored bosutinib vs. imatinib, particularly more in Asian (odds ratio [OR], 2.28; 95% confidence interval [CI], 0.87-5.97) than non-Asian (OR, 1.43; 95% CI, 0.99-2.07) subpopulation. Grade 3/4 treatment-emergent adverse events were more frequent with bosutinib vs. imatinib (72.7% vs. 36.4%) but were manageable.

Study details: This study evaluated 536 patients (Asian, n=67; non-Asian, n=469) with newly diagnosed CML-CP from the phase 3 BFORE trial randomly allocated to either bosutinib or imatinib.

Disclosures: This study was sponsored by Pfizer. The lead author and some of his coinvestigators reported advisory roles, speaker fees, owning stock in, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies, including Pfizer.

Source: Chuah C et al. Int J Hematol. 2021 Apr 13. doi: 10.1007/s12185-021-03144-4.

Key clinical point: Bosutinib was more effective than imatinib as first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) with manageable toxicity, particularly in the Asian subpopulation of BFORE trial.

Major finding: Rates of major molecular response favored bosutinib vs. imatinib, particularly more in Asian (odds ratio [OR], 2.28; 95% confidence interval [CI], 0.87-5.97) than non-Asian (OR, 1.43; 95% CI, 0.99-2.07) subpopulation. Grade 3/4 treatment-emergent adverse events were more frequent with bosutinib vs. imatinib (72.7% vs. 36.4%) but were manageable.

Study details: This study evaluated 536 patients (Asian, n=67; non-Asian, n=469) with newly diagnosed CML-CP from the phase 3 BFORE trial randomly allocated to either bosutinib or imatinib.

Disclosures: This study was sponsored by Pfizer. The lead author and some of his coinvestigators reported advisory roles, speaker fees, owning stock in, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies, including Pfizer.

Source: Chuah C et al. Int J Hematol. 2021 Apr 13. doi: 10.1007/s12185-021-03144-4.

Key clinical point: Bosutinib was more effective than imatinib as first-line treatment of newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) with manageable toxicity, particularly in the Asian subpopulation of BFORE trial.

Major finding: Rates of major molecular response favored bosutinib vs. imatinib, particularly more in Asian (odds ratio [OR], 2.28; 95% confidence interval [CI], 0.87-5.97) than non-Asian (OR, 1.43; 95% CI, 0.99-2.07) subpopulation. Grade 3/4 treatment-emergent adverse events were more frequent with bosutinib vs. imatinib (72.7% vs. 36.4%) but were manageable.

Study details: This study evaluated 536 patients (Asian, n=67; non-Asian, n=469) with newly diagnosed CML-CP from the phase 3 BFORE trial randomly allocated to either bosutinib or imatinib.

Disclosures: This study was sponsored by Pfizer. The lead author and some of his coinvestigators reported advisory roles, speaker fees, owning stock in, being an employee of, receiving support from, and/or consulting for various pharmaceutical companies, including Pfizer.

Source: Chuah C et al. Int J Hematol. 2021 Apr 13. doi: 10.1007/s12185-021-03144-4.

ENESTfreedom is an important study that set the current guidelines for TFR. The trial included 190 patients treated with front line nilotinib at 300mg twice daily for two years that had achieved an MR4.5, followed by one year of consolidation maintaining deep molecular response of at least MR4 were allowed to discontinued therapy. A recent 5 year update of the trial showed that 81/190 patients (42.6%) still remained on TFR (MR4) with 76 (40.0%) in MR4.5. From the patients who lost major molecular response (MMR) and were re-treated, 90/91 patients entering this phase (98.9%) regained MMR and 84/91 patients (92.3%) regained MR4.5. More important, no disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously, including a declined incidence of AEs at 96 weeks of the TFR follow up (with low incidence CV AEs), while an expected increase on those in the treatment re-initiation phase.  As previously has been described in other trials, Low Sokal risk score, BCR-ABL1 IS levels at 48 weeks of TFR and stable MR4.5 response for the first year of TFR were associated with higher TFR rates.

When looking at patients who can be candidates for TFR, it is important to take in consideration the likelihood of successful discontinuation and educate patients on certain factors that may contribute to good outcomes. The Australian CML group had previously reported the importance of the initial decline rate of BCR-ABL1 measured as halving time as an important factor associated to deep molecular response. The same group, in a very interesting publication, reported the impact of halving time as a strong predictor of sustained TFR post-tyrosine kinase inhibitor (TKI) cessation in CML patients treated with front line TKI therapies.

Out of 115 patients who attempted TFR and had ≥12 months of follow-up, 55% sustained TFR, defined as remaining in major molecular response off TKI therapy for 12 months, similar percentage seen in other studies. However, when the time taken for the BCR-ABL1 value to halve was applied, it became the strongest independent predictor of sustained TFR with 80% in patients with a halving time of <9.35 days (first quartile) compared with only 4% if the halving time was >21.85 days (last quartile) (P < .001). The e14a2 BCR-ABL1 transcript type and duration of TKI exposure before attempting TFR were also independent predictors of sustained TFR. However, the BCR-ABL1 value measured at 3 months of TKI was not an independent predictor of sustained TFR.

ENESTfreedom is an important study that set the current guidelines for TFR. The trial included 190 patients treated with front line nilotinib at 300mg twice daily for two years that had achieved an MR4.5, followed by one year of consolidation maintaining deep molecular response of at least MR4 were allowed to discontinued therapy. A recent 5 year update of the trial showed that 81/190 patients (42.6%) still remained on TFR (MR4) with 76 (40.0%) in MR4.5. From the patients who lost major molecular response (MMR) and were re-treated, 90/91 patients entering this phase (98.9%) regained MMR and 84/91 patients (92.3%) regained MR4.5. More important, no disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously, including a declined incidence of AEs at 96 weeks of the TFR follow up (with low incidence CV AEs), while an expected increase on those in the treatment re-initiation phase.  As previously has been described in other trials, Low Sokal risk score, BCR-ABL1 IS levels at 48 weeks of TFR and stable MR4.5 response for the first year of TFR were associated with higher TFR rates.

When looking at patients who can be candidates for TFR, it is important to take in consideration the likelihood of successful discontinuation and educate patients on certain factors that may contribute to good outcomes. The Australian CML group had previously reported the importance of the initial decline rate of BCR-ABL1 measured as halving time as an important factor associated to deep molecular response. The same group, in a very interesting publication, reported the impact of halving time as a strong predictor of sustained TFR post-tyrosine kinase inhibitor (TKI) cessation in CML patients treated with front line TKI therapies.

Out of 115 patients who attempted TFR and had ≥12 months of follow-up, 55% sustained TFR, defined as remaining in major molecular response off TKI therapy for 12 months, similar percentage seen in other studies. However, when the time taken for the BCR-ABL1 value to halve was applied, it became the strongest independent predictor of sustained TFR with 80% in patients with a halving time of <9.35 days (first quartile) compared with only 4% if the halving time was >21.85 days (last quartile) (P < .001). The e14a2 BCR-ABL1 transcript type and duration of TKI exposure before attempting TFR were also independent predictors of sustained TFR. However, the BCR-ABL1 value measured at 3 months of TKI was not an independent predictor of sustained TFR.

ENESTfreedom is an important study that set the current guidelines for TFR. The trial included 190 patients treated with front line nilotinib at 300mg twice daily for two years that had achieved an MR4.5, followed by one year of consolidation maintaining deep molecular response of at least MR4 were allowed to discontinued therapy. A recent 5 year update of the trial showed that 81/190 patients (42.6%) still remained on TFR (MR4) with 76 (40.0%) in MR4.5. From the patients who lost major molecular response (MMR) and were re-treated, 90/91 patients entering this phase (98.9%) regained MMR and 84/91 patients (92.3%) regained MR4.5. More important, no disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously, including a declined incidence of AEs at 96 weeks of the TFR follow up (with low incidence CV AEs), while an expected increase on those in the treatment re-initiation phase.  As previously has been described in other trials, Low Sokal risk score, BCR-ABL1 IS levels at 48 weeks of TFR and stable MR4.5 response for the first year of TFR were associated with higher TFR rates.

When looking at patients who can be candidates for TFR, it is important to take in consideration the likelihood of successful discontinuation and educate patients on certain factors that may contribute to good outcomes. The Australian CML group had previously reported the importance of the initial decline rate of BCR-ABL1 measured as halving time as an important factor associated to deep molecular response. The same group, in a very interesting publication, reported the impact of halving time as a strong predictor of sustained TFR post-tyrosine kinase inhibitor (TKI) cessation in CML patients treated with front line TKI therapies.

Out of 115 patients who attempted TFR and had ≥12 months of follow-up, 55% sustained TFR, defined as remaining in major molecular response off TKI therapy for 12 months, similar percentage seen in other studies. However, when the time taken for the BCR-ABL1 value to halve was applied, it became the strongest independent predictor of sustained TFR with 80% in patients with a halving time of <9.35 days (first quartile) compared with only 4% if the halving time was >21.85 days (last quartile) (P < .001). The e14a2 BCR-ABL1 transcript type and duration of TKI exposure before attempting TFR were also independent predictors of sustained TFR. However, the BCR-ABL1 value measured at 3 months of TKI was not an independent predictor of sustained TFR.

Key clinical point: Bosutinib was effective and safe as a second or subsequent line of treatment in a real-life cohort of elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) and multiple baseline comorbidities who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs).

Major finding: Overall, rates of cytogenic response, molecular response, 3-year event-free survival, and 3-year overall survival were 81.2%, 66.6%, 60.9%, and 86.4%, respectively. Grade 3/4 hematological and extra-hematological toxicities were reported in 6.9% and 18.8% of patients, respectively, with 11.9% of patients permanently discontinuing bosutinib because of toxicity.

Study details: Findings are from a retrospective analysis of 101 elderly (age, older than 65 years) patients with CML-CP treated with bosutinib in second or subsequent line. Patients switched to bosutinib because of intolerance (n=46) or resistance (n=55) to previous TKI therapies.

Disclosures: This study did not receive any type of funding. Some investigators including the lead author reported consulting for or receiving honoraria from various pharmaceutical companies.

Source: Latagliata R et al. Hematol Oncol. 2021 Feb 22. doi: 10.1002/hon.2851.

Key clinical point: Bosutinib was effective and safe as a second or subsequent line of treatment in a real-life cohort of elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) and multiple baseline comorbidities who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs).

Major finding: Overall, rates of cytogenic response, molecular response, 3-year event-free survival, and 3-year overall survival were 81.2%, 66.6%, 60.9%, and 86.4%, respectively. Grade 3/4 hematological and extra-hematological toxicities were reported in 6.9% and 18.8% of patients, respectively, with 11.9% of patients permanently discontinuing bosutinib because of toxicity.

Study details: Findings are from a retrospective analysis of 101 elderly (age, older than 65 years) patients with CML-CP treated with bosutinib in second or subsequent line. Patients switched to bosutinib because of intolerance (n=46) or resistance (n=55) to previous TKI therapies.

Disclosures: This study did not receive any type of funding. Some investigators including the lead author reported consulting for or receiving honoraria from various pharmaceutical companies.

Source: Latagliata R et al. Hematol Oncol. 2021 Feb 22. doi: 10.1002/hon.2851.

Key clinical point: Bosutinib was effective and safe as a second or subsequent line of treatment in a real-life cohort of elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) and multiple baseline comorbidities who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs).

Major finding: Overall, rates of cytogenic response, molecular response, 3-year event-free survival, and 3-year overall survival were 81.2%, 66.6%, 60.9%, and 86.4%, respectively. Grade 3/4 hematological and extra-hematological toxicities were reported in 6.9% and 18.8% of patients, respectively, with 11.9% of patients permanently discontinuing bosutinib because of toxicity.

Study details: Findings are from a retrospective analysis of 101 elderly (age, older than 65 years) patients with CML-CP treated with bosutinib in second or subsequent line. Patients switched to bosutinib because of intolerance (n=46) or resistance (n=55) to previous TKI therapies.

Disclosures: This study did not receive any type of funding. Some investigators including the lead author reported consulting for or receiving honoraria from various pharmaceutical companies.

Source: Latagliata R et al. Hematol Oncol. 2021 Feb 22. doi: 10.1002/hon.2851.