Clinical Edge Journal Scan Commentary: CML November 2021

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.