CML

Key clinical point: Cardiovascular risk stratification based on age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS), was feasible in patients with chronic myeloid leukemia (CML) treated with any tyrosine kinase inhibitors (TKI).

Major finding: During a median follow-up of 3.8 years, rates of major adverse cardiovascular events (MACE) in study-defined low-, intermediate-, and high-risk groups were 0%, 10%, and 19%, respectively. None of the patients reclassified from intermediate to low risk by CACS experienced MACE.

Study details: This retrospective study included 88 patients with CML treated with any TKI.

Disclosures: No specific source of funding was identified. Some investigators, including the lead author, reported receiving honoraria and consultancy fees or serving on advisory boards of various pharmaceutical companies.

Source: Baggio D et al. Intern Med J. 2021;51(10):1736-40 (Oct 18). Doi: 10.1111/imj.15517.

Key clinical point: Cardiovascular risk stratification based on age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS), was feasible in patients with chronic myeloid leukemia (CML) treated with any tyrosine kinase inhibitors (TKI).

Major finding: During a median follow-up of 3.8 years, rates of major adverse cardiovascular events (MACE) in study-defined low-, intermediate-, and high-risk groups were 0%, 10%, and 19%, respectively. None of the patients reclassified from intermediate to low risk by CACS experienced MACE.

Study details: This retrospective study included 88 patients with CML treated with any TKI.

Disclosures: No specific source of funding was identified. Some investigators, including the lead author, reported receiving honoraria and consultancy fees or serving on advisory boards of various pharmaceutical companies.

Source: Baggio D et al. Intern Med J. 2021;51(10):1736-40 (Oct 18). Doi: 10.1111/imj.15517.

Key clinical point: Cardiovascular risk stratification based on age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS), was feasible in patients with chronic myeloid leukemia (CML) treated with any tyrosine kinase inhibitors (TKI).

Major finding: During a median follow-up of 3.8 years, rates of major adverse cardiovascular events (MACE) in study-defined low-, intermediate-, and high-risk groups were 0%, 10%, and 19%, respectively. None of the patients reclassified from intermediate to low risk by CACS experienced MACE.

Study details: This retrospective study included 88 patients with CML treated with any TKI.

Disclosures: No specific source of funding was identified. Some investigators, including the lead author, reported receiving honoraria and consultancy fees or serving on advisory boards of various pharmaceutical companies.

Source: Baggio D et al. Intern Med J. 2021;51(10):1736-40 (Oct 18). Doi: 10.1111/imj.15517.

Key clinical point: Compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence.

Major finding: A 90-day imatinib pill-count adherence of 100% vs. 90% increased the probabilities of achieving complete hematological response by 2.25-fold (probability of treatment response [pTR] 0.8416 vs. 0.3746), complete cytogenic response by 2.24-fold (pTR 0.8335 vs. 0.3714), major molecular response by 1.95-fold (pTR 0.7698 vs. 0.3938), and optimal response by 2.35-fold (pTR 0.8236 vs. 0.3512).

Study details: Findings are from a post hoc analysis of the ADAGIO study including 169 patients with CML.

Disclosures: This study did not receive any specific funding. Some investigators reported being equity shareholders and employees of or receiving honoraria from various sources including Novartis which funded the ADAGIO study.

Source: Obeng-Kusi M et al. Leuk Res. 2021;111:106734 (Oct 21). Doi: 10.1016/j.leukres.2021.106734.

Key clinical point: Compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence.

Major finding: A 90-day imatinib pill-count adherence of 100% vs. 90% increased the probabilities of achieving complete hematological response by 2.25-fold (probability of treatment response [pTR] 0.8416 vs. 0.3746), complete cytogenic response by 2.24-fold (pTR 0.8335 vs. 0.3714), major molecular response by 1.95-fold (pTR 0.7698 vs. 0.3938), and optimal response by 2.35-fold (pTR 0.8236 vs. 0.3512).

Study details: Findings are from a post hoc analysis of the ADAGIO study including 169 patients with CML.

Disclosures: This study did not receive any specific funding. Some investigators reported being equity shareholders and employees of or receiving honoraria from various sources including Novartis which funded the ADAGIO study.

Source: Obeng-Kusi M et al. Leuk Res. 2021;111:106734 (Oct 21). Doi: 10.1016/j.leukres.2021.106734.

Key clinical point: Compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence.

Major finding: A 90-day imatinib pill-count adherence of 100% vs. 90% increased the probabilities of achieving complete hematological response by 2.25-fold (probability of treatment response [pTR] 0.8416 vs. 0.3746), complete cytogenic response by 2.24-fold (pTR 0.8335 vs. 0.3714), major molecular response by 1.95-fold (pTR 0.7698 vs. 0.3938), and optimal response by 2.35-fold (pTR 0.8236 vs. 0.3512).

Study details: Findings are from a post hoc analysis of the ADAGIO study including 169 patients with CML.

Disclosures: This study did not receive any specific funding. Some investigators reported being equity shareholders and employees of or receiving honoraria from various sources including Novartis which funded the ADAGIO study.

Source: Obeng-Kusi M et al. Leuk Res. 2021;111:106734 (Oct 21). Doi: 10.1016/j.leukres.2021.106734.

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

A version of this article first appeared on Medscape.com.

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

A version of this article first appeared on Medscape.com.

A number of late-phase clinical trials in leukemia have opened in recent months. Maybe one of your patients could benefit from being enrolled.

Adults and children with acute or chronic leukemias

A phase 2 study partnering with the National Marrow Donor Program is seeking individuals aged 1-65 years with lymphoma or one of the following leukemias: “acute leukemia”, acute lymphoblastic (ALL), acute myelogenous (AML), mixed-phenotype acute, chronic myelogenous (CML), and chronic lymphocytic (CLL). Researchers hope to find a way to improve outcomes of hematopoietic-cell transplantation from mismatched, unrelated donors. Participants will receive the transplant and one of seven drug regimens and will be followed for a year. The trial plans to enroll 180 people and began recruiting on Sept. 30 in California, New York, and Virginia. The primary outcome is overall survival (OS). Quality of life (QoL) will not be measured.

Mast-cell leukemia (MCL)

Adults with MCL are sought for a phase 2 study of bezuclastinib, an experimental tyrosine-kinase inhibitor (TKI) called CGT9486. CGT9486 blocks the activity of a mutated version of tyrosine-kinase receptor KIT, called KIT D816V, which is known to cause systemic mastocytosis. Participants will receive oral CGT9486 daily for up to 18 months. The study opened in October, aiming for 140 participants with any advanced systemic mastocytoses (including MCL) at sites in California, Florida, Massachusetts, New York, Ohio, Texas, and Utah. OS and QoL will be tracked.

Previously Treated CLL/Small Lymphocytic Lymphoma (SLL)

Patients with CLL/SLL who have progressed on previous therapy can join a phase 3 study of another experimental oral TIK, pirtobrutinib, this time targeting Bruton’s tyrosine kinase (BTK). BTK plays a key role in the lifecycle of white blood cells. Participants will receive either “fixed-duration” pirtobrutinib plus venetoclax (Venclexta) and rituximab (Ruxience, Riabni, Truxima, Rituxan, MabThera) or the venetoclax-rituximab combo only, for up to 5 years. Investigators started recruiting in September, aiming for 600 participants across Florida, Louisiana, Missouri, New York, and Tennessee. Progression-free survival is the primary outcome; OS is a secondary outcome and QoL will not be tracked.

High-grade myeloid cancers with measurable residual disease

Patients with AML, myelodysplastic syndrome with excess blasts-2 or myeloid neoplasm, and whose original disease is still present, are eligible for a phase 2 study of CPX-351 (daunorubicin-cytarabine, Vyxeos). The intravenous chemotherapy was approved in 2017 for certain types of AML. The goal of this study is to determine if pretreatment with CPX-351 improves the outcome of donor stem-cell transplantation. Patients will either undergo immediate transplantation or receive CPX-351 for up to 10 days followed 60 days later by the transplant. The study, being conducted at the Fred Hutchinson Cancer Research Center in Seattle, started recruiting 130 patients in August. The primary outcome is OS; QoL will not be tracked.

Newly diagnosed Philadelphia-negative ALL

Patients aged 22 or older with Philadelphia-negative ALL who have not received chemotherapy or radiation therapy are invited to join a trial of calaspargase pegol (Asparlas). The therapy was approved in 2018 for ALL in children and young adults (1 month to 21 years). The aim of this study is to confirm the recommended doses and evaluate the drug’s safety and pharmacodynamics in adults over aged 21. Each participant will receive six 2-hour infusions of calaspargase pegol over several months. The primary outcomes are safety and drug activity; OS is a secondary outcome and QoL will not be measured. The study opened on July 7 and aims to recruit 122 participants in 11 states.

Untreated adults with TP53-mutant AML

Adult patients with previously untreated AML who have at least one TP53 gene mutation are sought for a phase 3 study of magrolimab, an investigational anti-CD47 monoclonal antibody. Participants will be treated for up to 27 months with either magrolimab plus azacytidine (Vidaza), venetoclax plus azacytidine (patients deemed “appropriate for nonintensive therapy”), or standard chemotherapy (those “appropriate for intensive therapy”). In patients who received nonintensive therapy, OS is the primary outcome; OS in all participants is a secondary outcome, and QoL won’t be assessed. The trial opened in July and aims to recruit 346 individuals in Hong Kong, Australia, and the United States (California, Missouri, Oklahoma, Pennsylvania, South Carolina, and Texas).

All trial information is from the U.S. National Library of Medicine, National Institutes of Health.

A version of this article first appeared on Medscape.com.

In the new era of the COVID-19 pandemic, patients and physicians still struggle to see how different hematologic conditions may be affected by this viral infection. Although it has been well reported that COVID-19 may not be as lethal in chronic myeloid leukemia (CML) as other malignancies, patients still may be at risk of bad outcomes. A recent publication by Breccia et al¹collected retrospective information on more than 8000 CML patients followed at different institutions in Italy up to January 2021. The authors recorded 217 patients (2.5%) who were SARS-CO-V2 (COVID-19) positive. More than half of the patients had concomitant comorbidities. Almost 80% were quarantined while the rest required hospitalization, although only 3.6 required intensive care unit care. Twelve patients died, which represents 0.13% of the whole cohort. The main predisposing factors were age > 65 years and cardiovascular disorders, similar to that the general population.  Most of patients continue tyrosine kinase inhibitor (TKI) therapy during the infection.

While the introduction of TKI for the treatment of CML make the number of allogenic transplants decrease significantly due the high mortality in comparison with TKI therapy, it is still an option for certain patients who failed multiple TKI treatments or progressed to more advanced phases of the disease. Although it has already been described that the introduction of imatinib did not affect outcomes for patients that require this therapeutic option, there was not much data about the effect of second generation TKIs. In a publication by Masouridi-Levrat S et al² the authors examine the effect of second generation TKIs in a prospective non-interventional study performed by the European Group for Blood and Marrow Transplantation on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) from 2009 to 2013. Less than 40% of patients received the transplant in the chronic phase while the rest were in accelerated or blast phase. With a median follow-up of 37 months, 8% of patients developed either primary or secondary graft failure, 34% acute graft-versus-host disease (GvHD), and 60% chronic GvHD. The non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56%, and relapse-free survival 40% at 5 years. All these data showed the feasibility of this procedure in patients treated with second generation TKIs with similar post-transplant complications in TKI naive patients or patients treated with imatinib.

Patients under therapy with TKIs may frequently present with elevations of creatine kinase (CK), thought to be in some cases related with the classical associations with muscle and joint pain that is also a common side effect. However the long run effect on treatment outcomes has not been well studied. Bankar A et al.³ recently reported on the relation between CK elevations and overall survival (OS) and event free survival (EFS). Interestingly CK elevations secondary to first or second generation TKIs were associated with a better OS and EFS. As expected, high Sokal score patients had a worse OS and EFS.

References

1. Breccia M et al. COVID-19 infection in chronic myeloid leukaemia after one year of the pandemic in Italy. A Campus CML report. Br J Haematol. 2021 Oct 11.
2. Masouridi-Levrat S et al. Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors: a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT. Bone Marrow Transplant. 2021 Oct 1.
3. Bankar A, Lipton JH. Association of creatine kinase elevation with clinical outcomes in chronic myeloid leukemia: a retrospective cohort study Leuk Lymphoma. 2021 Sep 8.

In the new era of the COVID-19 pandemic, patients and physicians still struggle to see how different hematologic conditions may be affected by this viral infection. Although it has been well reported that COVID-19 may not be as lethal in chronic myeloid leukemia (CML) as other malignancies, patients still may be at risk of bad outcomes. A recent publication by Breccia et al¹collected retrospective information on more than 8000 CML patients followed at different institutions in Italy up to January 2021. The authors recorded 217 patients (2.5%) who were SARS-CO-V2 (COVID-19) positive. More than half of the patients had concomitant comorbidities. Almost 80% were quarantined while the rest required hospitalization, although only 3.6 required intensive care unit care. Twelve patients died, which represents 0.13% of the whole cohort. The main predisposing factors were age > 65 years and cardiovascular disorders, similar to that the general population.  Most of patients continue tyrosine kinase inhibitor (TKI) therapy during the infection.

While the introduction of TKI for the treatment of CML make the number of allogenic transplants decrease significantly due the high mortality in comparison with TKI therapy, it is still an option for certain patients who failed multiple TKI treatments or progressed to more advanced phases of the disease. Although it has already been described that the introduction of imatinib did not affect outcomes for patients that require this therapeutic option, there was not much data about the effect of second generation TKIs. In a publication by Masouridi-Levrat S et al² the authors examine the effect of second generation TKIs in a prospective non-interventional study performed by the European Group for Blood and Marrow Transplantation on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) from 2009 to 2013. Less than 40% of patients received the transplant in the chronic phase while the rest were in accelerated or blast phase. With a median follow-up of 37 months, 8% of patients developed either primary or secondary graft failure, 34% acute graft-versus-host disease (GvHD), and 60% chronic GvHD. The non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56%, and relapse-free survival 40% at 5 years. All these data showed the feasibility of this procedure in patients treated with second generation TKIs with similar post-transplant complications in TKI naive patients or patients treated with imatinib.

Patients under therapy with TKIs may frequently present with elevations of creatine kinase (CK), thought to be in some cases related with the classical associations with muscle and joint pain that is also a common side effect. However the long run effect on treatment outcomes has not been well studied. Bankar A et al.³ recently reported on the relation between CK elevations and overall survival (OS) and event free survival (EFS). Interestingly CK elevations secondary to first or second generation TKIs were associated with a better OS and EFS. As expected, high Sokal score patients had a worse OS and EFS.

References

1. Breccia M et al. COVID-19 infection in chronic myeloid leukaemia after one year of the pandemic in Italy. A Campus CML report. Br J Haematol. 2021 Oct 11.
2. Masouridi-Levrat S et al. Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors: a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT. Bone Marrow Transplant. 2021 Oct 1.
3. Bankar A, Lipton JH. Association of creatine kinase elevation with clinical outcomes in chronic myeloid leukemia: a retrospective cohort study Leuk Lymphoma. 2021 Sep 8.

In the new era of the COVID-19 pandemic, patients and physicians still struggle to see how different hematologic conditions may be affected by this viral infection. Although it has been well reported that COVID-19 may not be as lethal in chronic myeloid leukemia (CML) as other malignancies, patients still may be at risk of bad outcomes. A recent publication by Breccia et al¹collected retrospective information on more than 8000 CML patients followed at different institutions in Italy up to January 2021. The authors recorded 217 patients (2.5%) who were SARS-CO-V2 (COVID-19) positive. More than half of the patients had concomitant comorbidities. Almost 80% were quarantined while the rest required hospitalization, although only 3.6 required intensive care unit care. Twelve patients died, which represents 0.13% of the whole cohort. The main predisposing factors were age > 65 years and cardiovascular disorders, similar to that the general population.  Most of patients continue tyrosine kinase inhibitor (TKI) therapy during the infection.

While the introduction of TKI for the treatment of CML make the number of allogenic transplants decrease significantly due the high mortality in comparison with TKI therapy, it is still an option for certain patients who failed multiple TKI treatments or progressed to more advanced phases of the disease. Although it has already been described that the introduction of imatinib did not affect outcomes for patients that require this therapeutic option, there was not much data about the effect of second generation TKIs. In a publication by Masouridi-Levrat S et al² the authors examine the effect of second generation TKIs in a prospective non-interventional study performed by the European Group for Blood and Marrow Transplantation on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) from 2009 to 2013. Less than 40% of patients received the transplant in the chronic phase while the rest were in accelerated or blast phase. With a median follow-up of 37 months, 8% of patients developed either primary or secondary graft failure, 34% acute graft-versus-host disease (GvHD), and 60% chronic GvHD. The non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56%, and relapse-free survival 40% at 5 years. All these data showed the feasibility of this procedure in patients treated with second generation TKIs with similar post-transplant complications in TKI naive patients or patients treated with imatinib.

Patients under therapy with TKIs may frequently present with elevations of creatine kinase (CK), thought to be in some cases related with the classical associations with muscle and joint pain that is also a common side effect. However the long run effect on treatment outcomes has not been well studied. Bankar A et al.³ recently reported on the relation between CK elevations and overall survival (OS) and event free survival (EFS). Interestingly CK elevations secondary to first or second generation TKIs were associated with a better OS and EFS. As expected, high Sokal score patients had a worse OS and EFS.

References

1. Breccia M et al. COVID-19 infection in chronic myeloid leukaemia after one year of the pandemic in Italy. A Campus CML report. Br J Haematol. 2021 Oct 11.
2. Masouridi-Levrat S et al. Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors: a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT. Bone Marrow Transplant. 2021 Oct 1.
3. Bankar A, Lipton JH. Association of creatine kinase elevation with clinical outcomes in chronic myeloid leukemia: a retrospective cohort study Leuk Lymphoma. 2021 Sep 8.

Key clinical point: The incidence of chronic myeloid leukemia (CML) has increased globally, but the declining death rate indicates improved treatment options. However, patient management, particularly among elderly patients, needs more attention.

Major finding: The incident cases of CML increased globally by 54.1% from 1990 to 2019. The overall age-standardized death rate declined by 2.55% per year, and disease-adjusted life years (DALY) decreased by 2.69% per year. However, patients aged 70-84 years accounted for higher CML incidence and death cases. Smoking was the biggest risk factor for CML-related DALY (12.2%).

Study details: This study used annual data on the CML burden in 204 countries and regions from 1990 to 2019.

Disclosures: This study was supported by the National Natural Science Foundation of China, Taishan Scholars Program, and Clinical Research Project of Shandong University. The authors declared no conflict of interests.

Source: Hu Y et al. JCO Glob Oncol. 2021 (Sep 30);7:1429-1441. doi: 10.1200/GO.21.00194.

Key clinical point: The incidence of chronic myeloid leukemia (CML) has increased globally, but the declining death rate indicates improved treatment options. However, patient management, particularly among elderly patients, needs more attention.

Major finding: The incident cases of CML increased globally by 54.1% from 1990 to 2019. The overall age-standardized death rate declined by 2.55% per year, and disease-adjusted life years (DALY) decreased by 2.69% per year. However, patients aged 70-84 years accounted for higher CML incidence and death cases. Smoking was the biggest risk factor for CML-related DALY (12.2%).

Study details: This study used annual data on the CML burden in 204 countries and regions from 1990 to 2019.

Disclosures: This study was supported by the National Natural Science Foundation of China, Taishan Scholars Program, and Clinical Research Project of Shandong University. The authors declared no conflict of interests.

Source: Hu Y et al. JCO Glob Oncol. 2021 (Sep 30);7:1429-1441. doi: 10.1200/GO.21.00194.

Key clinical point: The incidence of chronic myeloid leukemia (CML) has increased globally, but the declining death rate indicates improved treatment options. However, patient management, particularly among elderly patients, needs more attention.

Major finding: The incident cases of CML increased globally by 54.1% from 1990 to 2019. The overall age-standardized death rate declined by 2.55% per year, and disease-adjusted life years (DALY) decreased by 2.69% per year. However, patients aged 70-84 years accounted for higher CML incidence and death cases. Smoking was the biggest risk factor for CML-related DALY (12.2%).

Study details: This study used annual data on the CML burden in 204 countries and regions from 1990 to 2019.

Disclosures: This study was supported by the National Natural Science Foundation of China, Taishan Scholars Program, and Clinical Research Project of Shandong University. The authors declared no conflict of interests.

Source: Hu Y et al. JCO Glob Oncol. 2021 (Sep 30);7:1429-1441. doi: 10.1200/GO.21.00194.

Key clinical point: Frontline treatment with dasatinib was effective, with an acceptable safety profile in older patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Overall, 93.3%, 77.7%, and 53.3% of patients achieved a complete cytogenic response, major molecular response, and deep molecular response, respectively. At 36 months, cumulative event-free survival and overall survival were 64.7% and 82.3%, respectively. Grade 3 and 4 adverse events were observed in 13.3% and 26.6% of patients, respectively. Treatment discontinuation and dasatinib dose reduction was reported in 20.0% and 53.3% of patients, respectively.

Study details: This retrospective study included 45 older (age ≥75 years) patients with newly diagnosed CML-CP treated with frontline dasatinib followed up for a median duration of 42.6 months.

Disclosures: No source of funding was identified. Some investigators, including the lead author, reported receiving honoraria from various pharmaceutical companies.

Source: Stagno F et al. Acta Oncol. 2021;69(11):1527-1533. doi: 10.1080/0284186X.2021.1971292.

Key clinical point: Frontline treatment with dasatinib was effective, with an acceptable safety profile in older patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Overall, 93.3%, 77.7%, and 53.3% of patients achieved a complete cytogenic response, major molecular response, and deep molecular response, respectively. At 36 months, cumulative event-free survival and overall survival were 64.7% and 82.3%, respectively. Grade 3 and 4 adverse events were observed in 13.3% and 26.6% of patients, respectively. Treatment discontinuation and dasatinib dose reduction was reported in 20.0% and 53.3% of patients, respectively.

Study details: This retrospective study included 45 older (age ≥75 years) patients with newly diagnosed CML-CP treated with frontline dasatinib followed up for a median duration of 42.6 months.

Disclosures: No source of funding was identified. Some investigators, including the lead author, reported receiving honoraria from various pharmaceutical companies.

Source: Stagno F et al. Acta Oncol. 2021;69(11):1527-1533. doi: 10.1080/0284186X.2021.1971292.

Key clinical point: Frontline treatment with dasatinib was effective, with an acceptable safety profile in older patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Overall, 93.3%, 77.7%, and 53.3% of patients achieved a complete cytogenic response, major molecular response, and deep molecular response, respectively. At 36 months, cumulative event-free survival and overall survival were 64.7% and 82.3%, respectively. Grade 3 and 4 adverse events were observed in 13.3% and 26.6% of patients, respectively. Treatment discontinuation and dasatinib dose reduction was reported in 20.0% and 53.3% of patients, respectively.

Study details: This retrospective study included 45 older (age ≥75 years) patients with newly diagnosed CML-CP treated with frontline dasatinib followed up for a median duration of 42.6 months.

Disclosures: No source of funding was identified. Some investigators, including the lead author, reported receiving honoraria from various pharmaceutical companies.

Source: Stagno F et al. Acta Oncol. 2021;69(11):1527-1533. doi: 10.1080/0284186X.2021.1971292.

Key clinical point: Treatment with the second-generation (2G) tyrosine kinase inhibitors (TKI) before allogeneic hematopoietic cell transplantation (allo-HCT) is feasible without any detrimental posttransplant outcomes or additional transplant-related toxicities in patients with chronic myeloid leukemia (CML).

Major finding: During a median follow-up of 37 months posttransplantation, 92% of patients had successful grafts, whereas 3% and 5% of patients experienced primary and secondary graft failure, respectively. At 5 years, nonrelapse mortality, chronic graft versus host disease, and overall survival were 24% (95% CI 19%-29%), 60% (95% CI 54%-66%), and 56% (95% CI 50%-62%), respectively.

Study details: This prospective study included 383 adult patients with CML previously treated with dasatinib (40%), nilotinib (17%), or sequential dasatinib and nilotinib with or without bosutinib or ponatinib (43%) who first underwent allo-HCT.

Disclosures: This study was supported by Novartis. Some investigators reported travel grants, honoraria, speaker fees, advisory board membership, or clinical trial independent data monitoring committee membership with various pharmaceutical companies, including Novartis.

Source: Masouridi-Levrat S et al. Bone Marrow Transplant. 2021 Oct 1. doi: 10.1038/s41409-021-01472-x.

Key clinical point: Treatment with the second-generation (2G) tyrosine kinase inhibitors (TKI) before allogeneic hematopoietic cell transplantation (allo-HCT) is feasible without any detrimental posttransplant outcomes or additional transplant-related toxicities in patients with chronic myeloid leukemia (CML).

Major finding: During a median follow-up of 37 months posttransplantation, 92% of patients had successful grafts, whereas 3% and 5% of patients experienced primary and secondary graft failure, respectively. At 5 years, nonrelapse mortality, chronic graft versus host disease, and overall survival were 24% (95% CI 19%-29%), 60% (95% CI 54%-66%), and 56% (95% CI 50%-62%), respectively.

Study details: This prospective study included 383 adult patients with CML previously treated with dasatinib (40%), nilotinib (17%), or sequential dasatinib and nilotinib with or without bosutinib or ponatinib (43%) who first underwent allo-HCT.

Disclosures: This study was supported by Novartis. Some investigators reported travel grants, honoraria, speaker fees, advisory board membership, or clinical trial independent data monitoring committee membership with various pharmaceutical companies, including Novartis.

Source: Masouridi-Levrat S et al. Bone Marrow Transplant. 2021 Oct 1. doi: 10.1038/s41409-021-01472-x.

Key clinical point: Treatment with the second-generation (2G) tyrosine kinase inhibitors (TKI) before allogeneic hematopoietic cell transplantation (allo-HCT) is feasible without any detrimental posttransplant outcomes or additional transplant-related toxicities in patients with chronic myeloid leukemia (CML).

Major finding: During a median follow-up of 37 months posttransplantation, 92% of patients had successful grafts, whereas 3% and 5% of patients experienced primary and secondary graft failure, respectively. At 5 years, nonrelapse mortality, chronic graft versus host disease, and overall survival were 24% (95% CI 19%-29%), 60% (95% CI 54%-66%), and 56% (95% CI 50%-62%), respectively.

Study details: This prospective study included 383 adult patients with CML previously treated with dasatinib (40%), nilotinib (17%), or sequential dasatinib and nilotinib with or without bosutinib or ponatinib (43%) who first underwent allo-HCT.

Disclosures: This study was supported by Novartis. Some investigators reported travel grants, honoraria, speaker fees, advisory board membership, or clinical trial independent data monitoring committee membership with various pharmaceutical companies, including Novartis.

Source: Masouridi-Levrat S et al. Bone Marrow Transplant. 2021 Oct 1. doi: 10.1038/s41409-021-01472-x.

Key clinical point: In real-life settings, patients with chronic myeloid leukemia (CML) in accelerated or chronic phase treated with new-generation tyrosine kinase inhibitor (NG-TKI) therapy in first line were more likely to achieve major molecular response (MMR) vs. those treated with imatinib.

Major finding: Patients receiving NG-TKI vs. imatinib were more likely to achieve MMR (77% vs. 61%; hazard ratio 1.88; 95% CI 1.35-2.61).

Study details: Findings are from a retrospective, population-based study including 507 adult patients with chronic or accelerated phase CML treated first with either imatinib (n = 388) or NG-TKI (nilotinib, n = 90; dasatinib, n = 24; bosutinib, n = 3; ponatinib, n = 2).

Disclosures: This study was funded by Force Hémato with the support of Novartis and supported by La Ligue Contre le Cancer. P Cony-Makhoul reported grants from Force Hémato. Other authors declared no conflict of interests.

Source: Canet J et al. Cancer Med 2021 Sep 22. doi: 10.1002/cam4.4186.

Key clinical point: In real-life settings, patients with chronic myeloid leukemia (CML) in accelerated or chronic phase treated with new-generation tyrosine kinase inhibitor (NG-TKI) therapy in first line were more likely to achieve major molecular response (MMR) vs. those treated with imatinib.

Major finding: Patients receiving NG-TKI vs. imatinib were more likely to achieve MMR (77% vs. 61%; hazard ratio 1.88; 95% CI 1.35-2.61).

Study details: Findings are from a retrospective, population-based study including 507 adult patients with chronic or accelerated phase CML treated first with either imatinib (n = 388) or NG-TKI (nilotinib, n = 90; dasatinib, n = 24; bosutinib, n = 3; ponatinib, n = 2).

Disclosures: This study was funded by Force Hémato with the support of Novartis and supported by La Ligue Contre le Cancer. P Cony-Makhoul reported grants from Force Hémato. Other authors declared no conflict of interests.

Source: Canet J et al. Cancer Med 2021 Sep 22. doi: 10.1002/cam4.4186.

Key clinical point: In real-life settings, patients with chronic myeloid leukemia (CML) in accelerated or chronic phase treated with new-generation tyrosine kinase inhibitor (NG-TKI) therapy in first line were more likely to achieve major molecular response (MMR) vs. those treated with imatinib.

Major finding: Patients receiving NG-TKI vs. imatinib were more likely to achieve MMR (77% vs. 61%; hazard ratio 1.88; 95% CI 1.35-2.61).

Study details: Findings are from a retrospective, population-based study including 507 adult patients with chronic or accelerated phase CML treated first with either imatinib (n = 388) or NG-TKI (nilotinib, n = 90; dasatinib, n = 24; bosutinib, n = 3; ponatinib, n = 2).

Disclosures: This study was funded by Force Hémato with the support of Novartis and supported by La Ligue Contre le Cancer. P Cony-Makhoul reported grants from Force Hémato. Other authors declared no conflict of interests.

Source: Canet J et al. Cancer Med 2021 Sep 22. doi: 10.1002/cam4.4186.

Key clinical point: Frontline nilotinib vs. imatinib therapy showed a positive benefit-risk ratio in Japanese patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP) at 10 years of follow-up.

Major finding: At 10 years, a higher proportion of patients achieved major molecular response (MR) and MR4.5 in the 300 mg (86.2% and 65.5%) and 400 mg (78.3% and 69.6%) nilotinib arms compared to the imatinib (60.0% and 48.0%) arm. Cardiovascular adverse events (14.3% and 18.2% vs. 0.0%) were more frequent with 300 and 400 mg nilotinib vs. imatinib.

Study details: Findings are from a 10-year follow-up of a Japanese subgroup of patients with newly diagnosed Ph+ CML-CP from the phase 3 ENESTnd trial randomly assigned to receive either 300 mg nilotinib twice daily (n = 29), 400 mg nilotinib twice daily (n = 23), or 400 mg imatinib once daily (n = 25).

Disclosures: No funding source was identified other than medical writing assistance funded by Novartis Pharma KK. Some investigators, including the lead author, reported being employees of or receiving research support and personal fees from various sources, including Novartis.

Source: Nakamae H et al. Int J Hematol. 2021 Sep 11. doi: 10.1007/s12185-021-03216-5.

Key clinical point: Frontline nilotinib vs. imatinib therapy showed a positive benefit-risk ratio in Japanese patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP) at 10 years of follow-up.

Major finding: At 10 years, a higher proportion of patients achieved major molecular response (MR) and MR4.5 in the 300 mg (86.2% and 65.5%) and 400 mg (78.3% and 69.6%) nilotinib arms compared to the imatinib (60.0% and 48.0%) arm. Cardiovascular adverse events (14.3% and 18.2% vs. 0.0%) were more frequent with 300 and 400 mg nilotinib vs. imatinib.

Study details: Findings are from a 10-year follow-up of a Japanese subgroup of patients with newly diagnosed Ph+ CML-CP from the phase 3 ENESTnd trial randomly assigned to receive either 300 mg nilotinib twice daily (n = 29), 400 mg nilotinib twice daily (n = 23), or 400 mg imatinib once daily (n = 25).

Disclosures: No funding source was identified other than medical writing assistance funded by Novartis Pharma KK. Some investigators, including the lead author, reported being employees of or receiving research support and personal fees from various sources, including Novartis.

Source: Nakamae H et al. Int J Hematol. 2021 Sep 11. doi: 10.1007/s12185-021-03216-5.

Key clinical point: Frontline nilotinib vs. imatinib therapy showed a positive benefit-risk ratio in Japanese patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP) at 10 years of follow-up.

Major finding: At 10 years, a higher proportion of patients achieved major molecular response (MR) and MR4.5 in the 300 mg (86.2% and 65.5%) and 400 mg (78.3% and 69.6%) nilotinib arms compared to the imatinib (60.0% and 48.0%) arm. Cardiovascular adverse events (14.3% and 18.2% vs. 0.0%) were more frequent with 300 and 400 mg nilotinib vs. imatinib.

Study details: Findings are from a 10-year follow-up of a Japanese subgroup of patients with newly diagnosed Ph+ CML-CP from the phase 3 ENESTnd trial randomly assigned to receive either 300 mg nilotinib twice daily (n = 29), 400 mg nilotinib twice daily (n = 23), or 400 mg imatinib once daily (n = 25).

Disclosures: No funding source was identified other than medical writing assistance funded by Novartis Pharma KK. Some investigators, including the lead author, reported being employees of or receiving research support and personal fees from various sources, including Novartis.

Source: Nakamae H et al. Int J Hematol. 2021 Sep 11. doi: 10.1007/s12185-021-03216-5.

Key clinical point: Considering inadequate representation of real-world patients (RWP) with chronic-phase chronic myeloid leukemia (CML-CP) in clinical trials, a “one size fits all” tyrosine kinase inhibitor (TKI) dosing regimen may not be apt.

Major finding: RWPs with 2 or more exclusion factors were more likely to achieve major molecular response at 3 months (adjusted relative risk [aRR] 1.89; P = .03) compared to those with no exclusion factors. They did achieve complete hematologic response at 1 month (aRR 0.80; P = .02), or have a higher adverse event-induced TKI dose reduction (aRR 1.53; P = .03) or shorter time to dose reduction (aRR 2.47; P = .005).

Study details: This retrospective study included 174 adult RWP with CML-CP treated with imatinib, dasatinib, nilotinib, or bosutinib for at least 30 days, with 0, 1, or 2 or more phase 3 clinical trial exclusion criterion.

Disclosures: This study was funded by the Eshelman Institute for Innovation at the University of North Carolina Eshelman School of Pharmacy. Some investigators reported receiving honoraria and research funding from or consulting for various pharmaceutical companies.

Source: Szeto AH et al. Ann Pharmacother. 2021 Sep 18. doi: 10.1177/10600280211044160.

Key clinical point: Considering inadequate representation of real-world patients (RWP) with chronic-phase chronic myeloid leukemia (CML-CP) in clinical trials, a “one size fits all” tyrosine kinase inhibitor (TKI) dosing regimen may not be apt.

Major finding: RWPs with 2 or more exclusion factors were more likely to achieve major molecular response at 3 months (adjusted relative risk [aRR] 1.89; P = .03) compared to those with no exclusion factors. They did achieve complete hematologic response at 1 month (aRR 0.80; P = .02), or have a higher adverse event-induced TKI dose reduction (aRR 1.53; P = .03) or shorter time to dose reduction (aRR 2.47; P = .005).

Study details: This retrospective study included 174 adult RWP with CML-CP treated with imatinib, dasatinib, nilotinib, or bosutinib for at least 30 days, with 0, 1, or 2 or more phase 3 clinical trial exclusion criterion.

Disclosures: This study was funded by the Eshelman Institute for Innovation at the University of North Carolina Eshelman School of Pharmacy. Some investigators reported receiving honoraria and research funding from or consulting for various pharmaceutical companies.

Source: Szeto AH et al. Ann Pharmacother. 2021 Sep 18. doi: 10.1177/10600280211044160.

Key clinical point: Considering inadequate representation of real-world patients (RWP) with chronic-phase chronic myeloid leukemia (CML-CP) in clinical trials, a “one size fits all” tyrosine kinase inhibitor (TKI) dosing regimen may not be apt.

Major finding: RWPs with 2 or more exclusion factors were more likely to achieve major molecular response at 3 months (adjusted relative risk [aRR] 1.89; P = .03) compared to those with no exclusion factors. They did achieve complete hematologic response at 1 month (aRR 0.80; P = .02), or have a higher adverse event-induced TKI dose reduction (aRR 1.53; P = .03) or shorter time to dose reduction (aRR 2.47; P = .005).

Study details: This retrospective study included 174 adult RWP with CML-CP treated with imatinib, dasatinib, nilotinib, or bosutinib for at least 30 days, with 0, 1, or 2 or more phase 3 clinical trial exclusion criterion.

Disclosures: This study was funded by the Eshelman Institute for Innovation at the University of North Carolina Eshelman School of Pharmacy. Some investigators reported receiving honoraria and research funding from or consulting for various pharmaceutical companies.

Source: Szeto AH et al. Ann Pharmacother. 2021 Sep 18. doi: 10.1177/10600280211044160.