AGA Clinical Practice Update: Management of bleeding gastric varices

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When classifying gastric varices during endoscopy, experts suggest not only describing their location but also their size and whether any high-risk stigmata, such as discolorations and platelet plugs, are present.

In a clinical practice update from the American Gastroenterological Association, Zachary Henry, MD, of the University of Virginia, Charlottesville, and associates also proposed an alternative nomenclature for locating gastric varices (GV). “In practice, most gastroenterologists use the Sarin classification with the main distinction being cardiofundal versus lesser curvature GV. However, the vascular supply and corresponding therapy for GV and esophageal varices are often different, so a merged classification, such as Sarin’s, can be problematic for therapeutic planning purposes,” they wrote in Clinical Gastroenterology and Hepatology, referring to the classification system published by Shiv K. Sarin, MD, DM, and colleagues. They suggested that a merged classification, such as Sarin’s, can be “problematic for therapeutic and planning purposes” because “the vascular supply and corresponding therapy for GV and [esophageal varices] are often different.” Instead, they advised that an “alternative nomenclature based on location within the stomach is clearer and facilitates correlation with vascular imaging.” Another approach is to add risk factors for bleeding, such as an estimate of variceal size and high-risk stigmata (discolored marks, platelet plugs), to Sarin classification.

Diagnosis and treatment of bleeding GV are complex, and multidisciplinary management by hepatologists, interventional radiologists, and interventional endoscopists is optimal, the experts wrote. Data and clinical guidelines do not support primary prophylaxis to prevent bleeding of GV. The authors offered an algorithm for initial management of suspected portal hypertensive GV bleeding based on both endoscopic and vascular anatomy; it includes assessment of circulatory and respiratory status, vasoactive drug administration, antibiotic prophylaxis, and more.

An early goal is confirming bleeding source and attempting to classify the bleeding site; this can be complicated by presence of intragastric blood that obscures the cardia and fundus and underlying GV. Further steps may include temporizing: “Temporizing measures to halt active bleeding are often not the definitive treatment of choice to prevent rebleeding from GV, whereas definitive measures such as endoscopic cyanoacrylate injection (ECI) or endovascular treatments are often not feasible in the acute, diagnostic setting.”

When definitive endoscopic treatment is preferred, ECI of bleeding GV is the therapy of choice because other approaches may be complicated by location and bleeding risk of GV, although band ligation may be appropriate in lesser curve GV. Specific ECI techniques have not been compared directly in studies, according to the update authors; however, “the specific cyanoacrylate agent should favor the fastest polymerization time to avoid embolization and inducing GV bleeding.” This has meant 4-carbon (butyl) preparations are preferred to 8-carbon (octyl) preparations, they noted.

After treatment, endoscopy is performed every 2-4 weeks so that the ECI can be repeated as needed until obliteration is complete. The experts suggested that, after eradication of GV, an endoscopic reevaluation within 3-6 months should be scheduled, then annually thereafter. Any de novo or recurrent GV during the long-term follow-up may require additional imaging and multidisciplinary exploration to determine potential mechanisms and need for alternative treatments, the authors advised.

According to the practice update, transjugular intrahepatic portosystemic shunt can be used when the GV is receiving significant inflow from the coronary vein or the patient has significant complications from portal hypertension. When TIPS is used, the experts suggest also performing endovascular sclerosis or direct embolization of GV, if possible. For patients with a gastrorenal shunt, balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding GV is considered optimal if local expertise is available and the patient lacks severe complications from portal hypertension. Endoscopy should be performed within 48 hours after BRTO to confirm obliteration of the vascular flow. If residual flow is detected, “cyanoacrylate injection should be performed,” the experts wrote. To confirm that GV are obliterated and check for any vascular complications, they suggest performing CT or MR within 4-6 weeks after BRTO and then as clinically indicated. In addition, surveillance endoscopy is important to identify and treat any esophageal varices that could have been worsened by increased portal pressures.

No funding sources were reported. The experts reported having no conflicts of interest.

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When classifying gastric varices during endoscopy, experts suggest not only describing their location but also their size and whether any high-risk stigmata, such as discolorations and platelet plugs, are present.

In a clinical practice update from the American Gastroenterological Association, Zachary Henry, MD, of the University of Virginia, Charlottesville, and associates also proposed an alternative nomenclature for locating gastric varices (GV). “In practice, most gastroenterologists use the Sarin classification with the main distinction being cardiofundal versus lesser curvature GV. However, the vascular supply and corresponding therapy for GV and esophageal varices are often different, so a merged classification, such as Sarin’s, can be problematic for therapeutic planning purposes,” they wrote in Clinical Gastroenterology and Hepatology, referring to the classification system published by Shiv K. Sarin, MD, DM, and colleagues. They suggested that a merged classification, such as Sarin’s, can be “problematic for therapeutic and planning purposes” because “the vascular supply and corresponding therapy for GV and [esophageal varices] are often different.” Instead, they advised that an “alternative nomenclature based on location within the stomach is clearer and facilitates correlation with vascular imaging.” Another approach is to add risk factors for bleeding, such as an estimate of variceal size and high-risk stigmata (discolored marks, platelet plugs), to Sarin classification.

Diagnosis and treatment of bleeding GV are complex, and multidisciplinary management by hepatologists, interventional radiologists, and interventional endoscopists is optimal, the experts wrote. Data and clinical guidelines do not support primary prophylaxis to prevent bleeding of GV. The authors offered an algorithm for initial management of suspected portal hypertensive GV bleeding based on both endoscopic and vascular anatomy; it includes assessment of circulatory and respiratory status, vasoactive drug administration, antibiotic prophylaxis, and more.

An early goal is confirming bleeding source and attempting to classify the bleeding site; this can be complicated by presence of intragastric blood that obscures the cardia and fundus and underlying GV. Further steps may include temporizing: “Temporizing measures to halt active bleeding are often not the definitive treatment of choice to prevent rebleeding from GV, whereas definitive measures such as endoscopic cyanoacrylate injection (ECI) or endovascular treatments are often not feasible in the acute, diagnostic setting.”

When definitive endoscopic treatment is preferred, ECI of bleeding GV is the therapy of choice because other approaches may be complicated by location and bleeding risk of GV, although band ligation may be appropriate in lesser curve GV. Specific ECI techniques have not been compared directly in studies, according to the update authors; however, “the specific cyanoacrylate agent should favor the fastest polymerization time to avoid embolization and inducing GV bleeding.” This has meant 4-carbon (butyl) preparations are preferred to 8-carbon (octyl) preparations, they noted.

After treatment, endoscopy is performed every 2-4 weeks so that the ECI can be repeated as needed until obliteration is complete. The experts suggested that, after eradication of GV, an endoscopic reevaluation within 3-6 months should be scheduled, then annually thereafter. Any de novo or recurrent GV during the long-term follow-up may require additional imaging and multidisciplinary exploration to determine potential mechanisms and need for alternative treatments, the authors advised.

According to the practice update, transjugular intrahepatic portosystemic shunt can be used when the GV is receiving significant inflow from the coronary vein or the patient has significant complications from portal hypertension. When TIPS is used, the experts suggest also performing endovascular sclerosis or direct embolization of GV, if possible. For patients with a gastrorenal shunt, balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding GV is considered optimal if local expertise is available and the patient lacks severe complications from portal hypertension. Endoscopy should be performed within 48 hours after BRTO to confirm obliteration of the vascular flow. If residual flow is detected, “cyanoacrylate injection should be performed,” the experts wrote. To confirm that GV are obliterated and check for any vascular complications, they suggest performing CT or MR within 4-6 weeks after BRTO and then as clinically indicated. In addition, surveillance endoscopy is important to identify and treat any esophageal varices that could have been worsened by increased portal pressures.

No funding sources were reported. The experts reported having no conflicts of interest.

When classifying gastric varices during endoscopy, experts suggest not only describing their location but also their size and whether any high-risk stigmata, such as discolorations and platelet plugs, are present.

In a clinical practice update from the American Gastroenterological Association, Zachary Henry, MD, of the University of Virginia, Charlottesville, and associates also proposed an alternative nomenclature for locating gastric varices (GV). “In practice, most gastroenterologists use the Sarin classification with the main distinction being cardiofundal versus lesser curvature GV. However, the vascular supply and corresponding therapy for GV and esophageal varices are often different, so a merged classification, such as Sarin’s, can be problematic for therapeutic planning purposes,” they wrote in Clinical Gastroenterology and Hepatology, referring to the classification system published by Shiv K. Sarin, MD, DM, and colleagues. They suggested that a merged classification, such as Sarin’s, can be “problematic for therapeutic and planning purposes” because “the vascular supply and corresponding therapy for GV and [esophageal varices] are often different.” Instead, they advised that an “alternative nomenclature based on location within the stomach is clearer and facilitates correlation with vascular imaging.” Another approach is to add risk factors for bleeding, such as an estimate of variceal size and high-risk stigmata (discolored marks, platelet plugs), to Sarin classification.

Diagnosis and treatment of bleeding GV are complex, and multidisciplinary management by hepatologists, interventional radiologists, and interventional endoscopists is optimal, the experts wrote. Data and clinical guidelines do not support primary prophylaxis to prevent bleeding of GV. The authors offered an algorithm for initial management of suspected portal hypertensive GV bleeding based on both endoscopic and vascular anatomy; it includes assessment of circulatory and respiratory status, vasoactive drug administration, antibiotic prophylaxis, and more.

An early goal is confirming bleeding source and attempting to classify the bleeding site; this can be complicated by presence of intragastric blood that obscures the cardia and fundus and underlying GV. Further steps may include temporizing: “Temporizing measures to halt active bleeding are often not the definitive treatment of choice to prevent rebleeding from GV, whereas definitive measures such as endoscopic cyanoacrylate injection (ECI) or endovascular treatments are often not feasible in the acute, diagnostic setting.”

When definitive endoscopic treatment is preferred, ECI of bleeding GV is the therapy of choice because other approaches may be complicated by location and bleeding risk of GV, although band ligation may be appropriate in lesser curve GV. Specific ECI techniques have not been compared directly in studies, according to the update authors; however, “the specific cyanoacrylate agent should favor the fastest polymerization time to avoid embolization and inducing GV bleeding.” This has meant 4-carbon (butyl) preparations are preferred to 8-carbon (octyl) preparations, they noted.

After treatment, endoscopy is performed every 2-4 weeks so that the ECI can be repeated as needed until obliteration is complete. The experts suggested that, after eradication of GV, an endoscopic reevaluation within 3-6 months should be scheduled, then annually thereafter. Any de novo or recurrent GV during the long-term follow-up may require additional imaging and multidisciplinary exploration to determine potential mechanisms and need for alternative treatments, the authors advised.

According to the practice update, transjugular intrahepatic portosystemic shunt can be used when the GV is receiving significant inflow from the coronary vein or the patient has significant complications from portal hypertension. When TIPS is used, the experts suggest also performing endovascular sclerosis or direct embolization of GV, if possible. For patients with a gastrorenal shunt, balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding GV is considered optimal if local expertise is available and the patient lacks severe complications from portal hypertension. Endoscopy should be performed within 48 hours after BRTO to confirm obliteration of the vascular flow. If residual flow is detected, “cyanoacrylate injection should be performed,” the experts wrote. To confirm that GV are obliterated and check for any vascular complications, they suggest performing CT or MR within 4-6 weeks after BRTO and then as clinically indicated. In addition, surveillance endoscopy is important to identify and treat any esophageal varices that could have been worsened by increased portal pressures.

No funding sources were reported. The experts reported having no conflicts of interest.

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Hyper-CVAD plus dasatinib improves survival in patients with CML-LBP

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Key clinical point: Hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) plus dasatinib therapy has improved clinical outcomes in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP) with survival comparable to that of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).

Major finding: Five-year overall (59% vs. 48%; P = .97) and progression-free (46% vs. 44%; P = .88) survival rates were similar in patients with CML-LBP and Ph-positive ALL.

Study details: This retrospective study included 23 and 62 patients with CML-LBP and newly diagnosed Ph-positive ALL, respectively, who were treated with hyper-CVAD plus dasatinib.

Disclosures: This work was supported in part by Cancer Center Support Grant to the University of Texas, MD Anderson. Some investigators reported honoraria, research grants, consulting fees, personal fees, patent and royalties, and membership on the board of directors or advisory committees from various pharmaceutical companies.

Source: Morita K et al. Cancer. 2021 Apr 6. doi: 10.1002/cncr.33539.

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Key clinical point: Hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) plus dasatinib therapy has improved clinical outcomes in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP) with survival comparable to that of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).

Major finding: Five-year overall (59% vs. 48%; P = .97) and progression-free (46% vs. 44%; P = .88) survival rates were similar in patients with CML-LBP and Ph-positive ALL.

Study details: This retrospective study included 23 and 62 patients with CML-LBP and newly diagnosed Ph-positive ALL, respectively, who were treated with hyper-CVAD plus dasatinib.

Disclosures: This work was supported in part by Cancer Center Support Grant to the University of Texas, MD Anderson. Some investigators reported honoraria, research grants, consulting fees, personal fees, patent and royalties, and membership on the board of directors or advisory committees from various pharmaceutical companies.

Source: Morita K et al. Cancer. 2021 Apr 6. doi: 10.1002/cncr.33539.

Key clinical point: Hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) plus dasatinib therapy has improved clinical outcomes in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP) with survival comparable to that of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).

Major finding: Five-year overall (59% vs. 48%; P = .97) and progression-free (46% vs. 44%; P = .88) survival rates were similar in patients with CML-LBP and Ph-positive ALL.

Study details: This retrospective study included 23 and 62 patients with CML-LBP and newly diagnosed Ph-positive ALL, respectively, who were treated with hyper-CVAD plus dasatinib.

Disclosures: This work was supported in part by Cancer Center Support Grant to the University of Texas, MD Anderson. Some investigators reported honoraria, research grants, consulting fees, personal fees, patent and royalties, and membership on the board of directors or advisory committees from various pharmaceutical companies.

Source: Morita K et al. Cancer. 2021 Apr 6. doi: 10.1002/cncr.33539.

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Cardiovascular evaluation warranted in all CML patients initiating nilotinib

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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.

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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.

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CML: Relative survival not on par with the general population even in the TKI era

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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.

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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.

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Gastrointestinal adverse event profiles may inform optimal TKI selection in CML-CP

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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.

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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.

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Bosutinib as effective as nilotinib and dasatinib in frontline treatment of CML-CP

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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.

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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.

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CML-CP: Investigating bone marrow LSC before TKI discontinuation could help maintain stable TFR

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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.

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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.

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CML-CP: TKI discontinuation effective even outside clinical trials

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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.

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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.

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CML: Imatinib as effective in the elderly as in the young but warrants management of adverse events

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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.

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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.

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SHM Converge Daily News -- Day 1

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Click here for the Wednesday issue of the SHM Converge Daily News newsletter.

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Click here for the Wednesday issue of the SHM Converge Daily News newsletter.

Click here for the Wednesday issue of the SHM Converge Daily News newsletter.

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