Clinical Edge Journal Scan

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

Two recently published studies added to our knowledge on the clinical benefit of gemtuzumab in patients with AML. The first study by Bouvier A et al demonstrated no survival benefit with the addition of gemtuzumab in patients with intermediate risk AML. The second study by Duncan et al was a retrospective study by the CIBMTR. That study demonstrated increased risk of VOD in pediatric patients who received gemtuzmab. However, overall survival and event free survival was similar in both groups. These results highlight the need for increased awareness post-transplant for the possibility of VOD, and also reduces concern regarding overall survival for patients receiving gemtuzumab.

Another study by the EBMT (Debaja et al) evaluated factors affecting the outcome of patients with AML receiving a second allogeneic HCT. Outcome was worse for patients not in CR and those with a short time from allo-HCT.  Overall survival was similar for patients receiving a MUD or haploidentical donor. Two year overall survival was 31% vs. 29% for patients receiving MUD vs. haploidentical allo-HCT. This study clearly expands options for patients receiving a second allo-HCT. In addition, a prior study by EBMT demonstrated no difference in overall survival between patients receiving same vs. different vs. haplo donor.

Finally, a large study by the CIBMTR (Percival et al) demonstrated that in AML patients, achieving CRi and having persistent MRD prior to transplantation were associated with worse outcome compared to CR with no evidence of MRD. The adjusted 5 year survival for patient with CR/MRD-ve, CR/MRD+ve, CRi/MRD-ve and CRi/MRD+ve was 52%, 37%, 44% and 34% respectively.

One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

Key clinical point: Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment strategy for patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant or intolerant to prior tyrosine kinase inhibitors (TKIs). However, better patient selection and posttransplant strategies are needed to mitigate the risk of relapse.

Major finding: Pooled rates of overall survival, disease-free survival, complete remission, and molecular response in adult allo-HCT recipients were 84% (95% confidence interval [CI], 59%-99%), 66% (95% CI, 59%-73%), 56% (95% CI, 30%-80%), and 88% (95% CI, 62%-98%), respectively. Pooled rates of nonrelapse mortality and relapse were 20% (95% CI, 15%-26%) and 19% (95% CI, 10%-28%), respectively.

Study details: This was a systematic review and meta-analysis of 9 studies including 439 patients with TKI-resistant or intolerant CML-CP who received allo-HCT.

Disclosures: No funding source was identified. MA Moustafa reported consulting for Acrotech Biopharma and MA Kharfan-Dabaja reported consulting for Pharmacyclics and Daiichi Sankyo. Other authors declared no conflicts of interest.

Source: Yassine F et al. Hematol Oncol Stem Cell Ther. 2021 Mar 11. doi: 10.1016/j.hemonc.2021.02.003.

Key clinical point: Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment strategy for patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant or intolerant to prior tyrosine kinase inhibitors (TKIs). However, better patient selection and posttransplant strategies are needed to mitigate the risk of relapse.

Major finding: Pooled rates of overall survival, disease-free survival, complete remission, and molecular response in adult allo-HCT recipients were 84% (95% confidence interval [CI], 59%-99%), 66% (95% CI, 59%-73%), 56% (95% CI, 30%-80%), and 88% (95% CI, 62%-98%), respectively. Pooled rates of nonrelapse mortality and relapse were 20% (95% CI, 15%-26%) and 19% (95% CI, 10%-28%), respectively.

Study details: This was a systematic review and meta-analysis of 9 studies including 439 patients with TKI-resistant or intolerant CML-CP who received allo-HCT.

Disclosures: No funding source was identified. MA Moustafa reported consulting for Acrotech Biopharma and MA Kharfan-Dabaja reported consulting for Pharmacyclics and Daiichi Sankyo. Other authors declared no conflicts of interest.

Source: Yassine F et al. Hematol Oncol Stem Cell Ther. 2021 Mar 11. doi: 10.1016/j.hemonc.2021.02.003.

Key clinical point: Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment strategy for patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant or intolerant to prior tyrosine kinase inhibitors (TKIs). However, better patient selection and posttransplant strategies are needed to mitigate the risk of relapse.

Major finding: Pooled rates of overall survival, disease-free survival, complete remission, and molecular response in adult allo-HCT recipients were 84% (95% confidence interval [CI], 59%-99%), 66% (95% CI, 59%-73%), 56% (95% CI, 30%-80%), and 88% (95% CI, 62%-98%), respectively. Pooled rates of nonrelapse mortality and relapse were 20% (95% CI, 15%-26%) and 19% (95% CI, 10%-28%), respectively.

Study details: This was a systematic review and meta-analysis of 9 studies including 439 patients with TKI-resistant or intolerant CML-CP who received allo-HCT.

Disclosures: No funding source was identified. MA Moustafa reported consulting for Acrotech Biopharma and MA Kharfan-Dabaja reported consulting for Pharmacyclics and Daiichi Sankyo. Other authors declared no conflicts of interest.

Source: Yassine F et al. Hematol Oncol Stem Cell Ther. 2021 Mar 11. doi: 10.1016/j.hemonc.2021.02.003.

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.

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: 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.