CML

Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.

One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.

Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.

Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
 

Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.

One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.

Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.

Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
 

Long term CML follow up clinical trials are quite important tool to monitor the late or new adverse side effects as well as to conform the efficacy in the long run of the drug tested. However, there are not so many examples on CML outside the IRIS trial. Recently, Kantarjian and collaborators had published the 10 years follow up on the ENESTnd trial that compared the use of two doses of nilotinib (300md bid and 400 mg bid) against imatinib (400mg qd). Once again, the study showed a higher cumulative molecular response rates (MMR: 77% vs 79% vs 62% and MR4.5:61% vs61% vs 39%) that translated in a higher proportion of patient candidates for TFR (48% vs 47% vs 29%). Furthermore, nilotinib was associated to lower rates of disease progression compare with imatinib. As previously described there were no differences in terms of PFS or OS between the three arms. In terms of toxicity, although the overall adverse effects were similar, a higher incidence of cardiovascular events were reported (16% vs 23% vs 3%). The incidence of these CVE on the nilotinib arm continue to occur at the same rate each year and were more associated with high and intermediate Framingham risk. Overall, the trial supports the use of nilotinib 300mg twice daily as front line therapy for CML for optimal long terms outcomes with a positive benefit-risk in the context of TFR as treatment goal.

One of the important aspects of the CVE secondary to second generation TKIs is the identification of high-risk populations as well as biomarkers that may help to prevent these episodes. In this regard, Italian investigators recently published a study of 369 patients treated with nilotinib where, besides stratification by the new coronary risk evaluation (SCORE), they measure the lipids levels at various times point since the initiation of therapy and identify cholesterol greater than 200mg/dL and LDL greater than 70 mg/dL as predictors factor for increased risk of CVE as well as a high SCORE risk. The authors suggest an aggressive follow up on lipids levels in patients taking nilotinib and the incorporation of cholesterol lowering medications.

Although the incidence of CVE has been more classically associated with nilotinib and ponatinib, more recent evidence suggests that the use of second generation TKIs in general can increase the risk of CVE in CML patients in comparison with the general population; however, it is hard to study the contribution of the disease itself. Leong and collaborators recently published a very large retrospective analysis of more than 4,000 CML patients that were age and sex matched with 42,000 controls without CML, showing that the incidence of these events is higher before and after the introduction of TKIs in 2001.

Javier Pinilla-Ibarz, MD, PhD
Senior Member
Lymphoma Section Head and
Director of Immunotherapy
Malignant Hematology Department
H. Lee Moffitt Cancer Center & Research Institute
 

Key clinical point: In 10-year follow-up of ENESTnd trial, nilotinib demonstrated benefits over imatinib for various clinical outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

Major finding: Cumulative 10-year rates of treatment-free remission eligibility and molecular response rate with nilotinib 300 mg and 400 mg vs. imatinib was 48.6% and 47.3% vs. 29.7% and 77.7% and 79.7% vs. 62.5%, respectively. Progression to accelerated (6 and 4 vs. 11) or blast (6 and 6 vs. 14) phase was lower with nilotinib 300 mg and 400 mg vs. imatinib, respectively. Overall, the frequency of adverse events was similar, but rates of cardiovascular events were higher with nilotinib.

Study details: ENESTnd, a phase 3 study, randomly allocated patients with newly diagnosed CML-CP to receive nilotinib 300 mg twice daily (n=282), nilotinib 400 mg twice daily (n=281), or imatinib 400 mg once daily (n=283).

Disclosures: The study was funded by Novartis Pharmaceuticals Corporation. The presenting author reported ties with Pharmaceuticals companies including Novartis. Some of the study investigators reported being an employee of, receiving grants, honoraria, support, and/or consulting for Novartis and other pharmaceutical companies.

Source: Kantarjian HM et al. Leukemia. 2021 Jan 7. doi: 10.1038/s41375-020-01111-2.

Key clinical point: In 10-year follow-up of ENESTnd trial, nilotinib demonstrated benefits over imatinib for various clinical outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

Major finding: Cumulative 10-year rates of treatment-free remission eligibility and molecular response rate with nilotinib 300 mg and 400 mg vs. imatinib was 48.6% and 47.3% vs. 29.7% and 77.7% and 79.7% vs. 62.5%, respectively. Progression to accelerated (6 and 4 vs. 11) or blast (6 and 6 vs. 14) phase was lower with nilotinib 300 mg and 400 mg vs. imatinib, respectively. Overall, the frequency of adverse events was similar, but rates of cardiovascular events were higher with nilotinib.

Study details: ENESTnd, a phase 3 study, randomly allocated patients with newly diagnosed CML-CP to receive nilotinib 300 mg twice daily (n=282), nilotinib 400 mg twice daily (n=281), or imatinib 400 mg once daily (n=283).

Disclosures: The study was funded by Novartis Pharmaceuticals Corporation. The presenting author reported ties with Pharmaceuticals companies including Novartis. Some of the study investigators reported being an employee of, receiving grants, honoraria, support, and/or consulting for Novartis and other pharmaceutical companies.

Source: Kantarjian HM et al. Leukemia. 2021 Jan 7. doi: 10.1038/s41375-020-01111-2.

Key clinical point: In 10-year follow-up of ENESTnd trial, nilotinib demonstrated benefits over imatinib for various clinical outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

Major finding: Cumulative 10-year rates of treatment-free remission eligibility and molecular response rate with nilotinib 300 mg and 400 mg vs. imatinib was 48.6% and 47.3% vs. 29.7% and 77.7% and 79.7% vs. 62.5%, respectively. Progression to accelerated (6 and 4 vs. 11) or blast (6 and 6 vs. 14) phase was lower with nilotinib 300 mg and 400 mg vs. imatinib, respectively. Overall, the frequency of adverse events was similar, but rates of cardiovascular events were higher with nilotinib.

Study details: ENESTnd, a phase 3 study, randomly allocated patients with newly diagnosed CML-CP to receive nilotinib 300 mg twice daily (n=282), nilotinib 400 mg twice daily (n=281), or imatinib 400 mg once daily (n=283).

Disclosures: The study was funded by Novartis Pharmaceuticals Corporation. The presenting author reported ties with Pharmaceuticals companies including Novartis. Some of the study investigators reported being an employee of, receiving grants, honoraria, support, and/or consulting for Novartis and other pharmaceutical companies.

Source: Kantarjian HM et al. Leukemia. 2021 Jan 7. doi: 10.1038/s41375-020-01111-2.

Key clinical point: Patients with chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors (TKIs) are at a greater risk for adverse cardiovascular events (ACEs) compared with the general population.

Major finding: From 2001 onwards, the risk for major ACEs (subdistribution hazard ratio [SHR], 1.27; 95% confidence interval [CI], 0.96-1.43) and cardiovascular death (SHR, 0.99; 95% CI, 0.84-1.18) was similar between patients with vs. without CML. However, before 2001, the risk for major ACE (SHR, 0.59; 95% CI, 0.46-0.76) and cardiovascular death (SHR, 0.43; 95% CI, 0.36-0.52) was lower in patients with vs. without CML.

Study details: A population-based retrospective study of 4,238 patients with CML who were age- and sex-matched with 42,380 controls without CML.

Disclosures: The study was funded by the Population Health Research Institute, McMaster University, and Institute of Clinical and Evaluative Sciences. The authors reported no conflicts of interest.

Source: Leong D et al. Heart. 2021 Jan 8. doi: 10.1136/heartjnl-2020-318251.

Key clinical point: Patients with chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors (TKIs) are at a greater risk for adverse cardiovascular events (ACEs) compared with the general population.

Major finding: From 2001 onwards, the risk for major ACEs (subdistribution hazard ratio [SHR], 1.27; 95% confidence interval [CI], 0.96-1.43) and cardiovascular death (SHR, 0.99; 95% CI, 0.84-1.18) was similar between patients with vs. without CML. However, before 2001, the risk for major ACE (SHR, 0.59; 95% CI, 0.46-0.76) and cardiovascular death (SHR, 0.43; 95% CI, 0.36-0.52) was lower in patients with vs. without CML.

Study details: A population-based retrospective study of 4,238 patients with CML who were age- and sex-matched with 42,380 controls without CML.

Disclosures: The study was funded by the Population Health Research Institute, McMaster University, and Institute of Clinical and Evaluative Sciences. The authors reported no conflicts of interest.

Source: Leong D et al. Heart. 2021 Jan 8. doi: 10.1136/heartjnl-2020-318251.

Key clinical point: Patients with chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors (TKIs) are at a greater risk for adverse cardiovascular events (ACEs) compared with the general population.

Major finding: From 2001 onwards, the risk for major ACEs (subdistribution hazard ratio [SHR], 1.27; 95% confidence interval [CI], 0.96-1.43) and cardiovascular death (SHR, 0.99; 95% CI, 0.84-1.18) was similar between patients with vs. without CML. However, before 2001, the risk for major ACE (SHR, 0.59; 95% CI, 0.46-0.76) and cardiovascular death (SHR, 0.43; 95% CI, 0.36-0.52) was lower in patients with vs. without CML.

Study details: A population-based retrospective study of 4,238 patients with CML who were age- and sex-matched with 42,380 controls without CML.

Disclosures: The study was funded by the Population Health Research Institute, McMaster University, and Institute of Clinical and Evaluative Sciences. The authors reported no conflicts of interest.

Source: Leong D et al. Heart. 2021 Jan 8. doi: 10.1136/heartjnl-2020-318251.

Key clinical point: High levels of cholesterol plasma and low-density lipoprotein (LDL) after 3 months of nilotinib initiation were associated with a higher risk for arterial occlusive events (AOEs) in patients with chronic myeloid leukemia (CML).

Major finding: Cholesterol plasma level greater than 200 mg/dL and LDL greater than 70 mg/dL after 3 months since nilotinib initiation was associated with a significantly higher risk of AOEs (hazard ratio, 3.5; P = .008).

Study details: Findings are from a retrospective study of 369 patients with CML treated with nilotinib.

Disclosures: The study was performed within the framework of the research project funded by P.O.R. SARDEGNA F.S.E. 2014-2020 - Asse III. The authors declared no conflicts of interest.

Source: Caocci G et al. Ann Hematol. 2021 Jan 3. doi: 10.1007/s00277-020-04392-w.

Key clinical point: High levels of cholesterol plasma and low-density lipoprotein (LDL) after 3 months of nilotinib initiation were associated with a higher risk for arterial occlusive events (AOEs) in patients with chronic myeloid leukemia (CML).

Major finding: Cholesterol plasma level greater than 200 mg/dL and LDL greater than 70 mg/dL after 3 months since nilotinib initiation was associated with a significantly higher risk of AOEs (hazard ratio, 3.5; P = .008).

Study details: Findings are from a retrospective study of 369 patients with CML treated with nilotinib.

Disclosures: The study was performed within the framework of the research project funded by P.O.R. SARDEGNA F.S.E. 2014-2020 - Asse III. The authors declared no conflicts of interest.

Source: Caocci G et al. Ann Hematol. 2021 Jan 3. doi: 10.1007/s00277-020-04392-w.

Key clinical point: High levels of cholesterol plasma and low-density lipoprotein (LDL) after 3 months of nilotinib initiation were associated with a higher risk for arterial occlusive events (AOEs) in patients with chronic myeloid leukemia (CML).

Major finding: Cholesterol plasma level greater than 200 mg/dL and LDL greater than 70 mg/dL after 3 months since nilotinib initiation was associated with a significantly higher risk of AOEs (hazard ratio, 3.5; P = .008).

Study details: Findings are from a retrospective study of 369 patients with CML treated with nilotinib.

Disclosures: The study was performed within the framework of the research project funded by P.O.R. SARDEGNA F.S.E. 2014-2020 - Asse III. The authors declared no conflicts of interest.

Source: Caocci G et al. Ann Hematol. 2021 Jan 3. doi: 10.1007/s00277-020-04392-w.

Key clinical point: Patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib showed superior 2-year adherence with second-line therapy dasatinib vs. nilotinib. Efficacy outcomes between both drugs were similar.

Major finding: Mean adherence calculated over 2 years was superior for dasatinib vs. nilotinib (0.91 vs. 0.82; P = .0043). Persistence for both drugs was 77%. At 2 years, 92% of patients were not in progression for both drugs (P = .02163).

Study details: This retrospective observational study evaluated 117 patients with CML treated with dasatinib (n = 70) or nilotinib (n = 47). Included patients showed resistance/intolerance to first-line treatment with imatinib.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Santoleri F et al. Curr Med Res Opin. 2021 Jan 16. doi: 10.1080/03007995.2021.1876006.

Key clinical point: Patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib showed superior 2-year adherence with second-line therapy dasatinib vs. nilotinib. Efficacy outcomes between both drugs were similar.

Major finding: Mean adherence calculated over 2 years was superior for dasatinib vs. nilotinib (0.91 vs. 0.82; P = .0043). Persistence for both drugs was 77%. At 2 years, 92% of patients were not in progression for both drugs (P = .02163).

Study details: This retrospective observational study evaluated 117 patients with CML treated with dasatinib (n = 70) or nilotinib (n = 47). Included patients showed resistance/intolerance to first-line treatment with imatinib.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Santoleri F et al. Curr Med Res Opin. 2021 Jan 16. doi: 10.1080/03007995.2021.1876006.

Key clinical point: Patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib showed superior 2-year adherence with second-line therapy dasatinib vs. nilotinib. Efficacy outcomes between both drugs were similar.

Major finding: Mean adherence calculated over 2 years was superior for dasatinib vs. nilotinib (0.91 vs. 0.82; P = .0043). Persistence for both drugs was 77%. At 2 years, 92% of patients were not in progression for both drugs (P = .02163).

Study details: This retrospective observational study evaluated 117 patients with CML treated with dasatinib (n = 70) or nilotinib (n = 47). Included patients showed resistance/intolerance to first-line treatment with imatinib.

Disclosures: The study did not receive any funding. The authors declared no conflicts of interest.

Source: Santoleri F et al. Curr Med Res Opin. 2021 Jan 16. doi: 10.1080/03007995.2021.1876006.

Key clinical point: Comparison of mortality rates highlights benefits of second-generation tyrosine kinase inhibitors (TKIs) in elderly patients aged 75 years or more with chronic myeloid leukemia in chronic phase (CML-CP). However, data need further confirmation in long-term studies.

Major finding: Mortality rates reduced in patients with CML-CP aged 75 years and more vs. the general population (−0.65%). The increased rate of mortality in patients with CP-CML in the age groups 0-29, 30-44, 45-59, and 60-74 years was 0.60%, 1.94%, 1.77%, and 1.43%, respectively.

Study details: A retrospective study of 2,315 patients with CP-CML treated with frontline second-generation TKIs.

Disclosures: No information on funding was available. The presenting author M Breccia reported honoraria from Novartis, Incyte, Pfizer, and Celgene. All other authors declared no conflicts of interest.

Source: Breccia M et al. Ann Hematol. 2021 Jan 7. doi: 10.1007/s00277-021-04406-1.

Key clinical point: Comparison of mortality rates highlights benefits of second-generation tyrosine kinase inhibitors (TKIs) in elderly patients aged 75 years or more with chronic myeloid leukemia in chronic phase (CML-CP). However, data need further confirmation in long-term studies.

Major finding: Mortality rates reduced in patients with CML-CP aged 75 years and more vs. the general population (−0.65%). The increased rate of mortality in patients with CP-CML in the age groups 0-29, 30-44, 45-59, and 60-74 years was 0.60%, 1.94%, 1.77%, and 1.43%, respectively.

Study details: A retrospective study of 2,315 patients with CP-CML treated with frontline second-generation TKIs.

Disclosures: No information on funding was available. The presenting author M Breccia reported honoraria from Novartis, Incyte, Pfizer, and Celgene. All other authors declared no conflicts of interest.

Source: Breccia M et al. Ann Hematol. 2021 Jan 7. doi: 10.1007/s00277-021-04406-1.

Key clinical point: Comparison of mortality rates highlights benefits of second-generation tyrosine kinase inhibitors (TKIs) in elderly patients aged 75 years or more with chronic myeloid leukemia in chronic phase (CML-CP). However, data need further confirmation in long-term studies.

Major finding: Mortality rates reduced in patients with CML-CP aged 75 years and more vs. the general population (−0.65%). The increased rate of mortality in patients with CP-CML in the age groups 0-29, 30-44, 45-59, and 60-74 years was 0.60%, 1.94%, 1.77%, and 1.43%, respectively.

Study details: A retrospective study of 2,315 patients with CP-CML treated with frontline second-generation TKIs.

Disclosures: No information on funding was available. The presenting author M Breccia reported honoraria from Novartis, Incyte, Pfizer, and Celgene. All other authors declared no conflicts of interest.

Source: Breccia M et al. Ann Hematol. 2021 Jan 7. doi: 10.1007/s00277-021-04406-1.

Key clinical point: Biomarkers can predict relapse in patients with chronic myeloid leukemia (CML) who are eligible for a controlled treatment interruption.

Major finding: Predictors of CML relapse after treatment interruptions were low levels of cytotoxic cells such as CD56+ with low expression of CD16 and CD94/NKG2 receptors and CD8± T cells expressing TCRγβ+; low expression of activating receptors on the surface of natural killer (NK) and NK T cells; impaired synthesis of proinflammatory cytokines or proteases from NK cells; and HLA-E*0103 homozygosis and KIR haplotype BX.

Study details: The data come from an observational, cross-sectional study of 93 patients with chronic phase CML and 20 age- and gender-matched controls. Among patients with CML, 45 were on treatment with tyrosine kinase inhibitors (TKIs), 27 on sustained treatment-free remission (off TKIs), 15 had a relapse, and 6 had newly diagnosed CML.

Disclosures: The study was funded by the Foundation for Biomedical Research of the Hospital Universitario Ramón y Cajal, the Spanish Ministry of Economy and Competitiveness, and the Spanish AIDS Research Network. The authors declared no conflicts of interest.

Source: Vigón L et al. J Clin Med. 2020 Dec 25. doi: 10.3390/jcm10010042.

Key clinical point: Biomarkers can predict relapse in patients with chronic myeloid leukemia (CML) who are eligible for a controlled treatment interruption.

Major finding: Predictors of CML relapse after treatment interruptions were low levels of cytotoxic cells such as CD56+ with low expression of CD16 and CD94/NKG2 receptors and CD8± T cells expressing TCRγβ+; low expression of activating receptors on the surface of natural killer (NK) and NK T cells; impaired synthesis of proinflammatory cytokines or proteases from NK cells; and HLA-E*0103 homozygosis and KIR haplotype BX.

Study details: The data come from an observational, cross-sectional study of 93 patients with chronic phase CML and 20 age- and gender-matched controls. Among patients with CML, 45 were on treatment with tyrosine kinase inhibitors (TKIs), 27 on sustained treatment-free remission (off TKIs), 15 had a relapse, and 6 had newly diagnosed CML.

Disclosures: The study was funded by the Foundation for Biomedical Research of the Hospital Universitario Ramón y Cajal, the Spanish Ministry of Economy and Competitiveness, and the Spanish AIDS Research Network. The authors declared no conflicts of interest.

Source: Vigón L et al. J Clin Med. 2020 Dec 25. doi: 10.3390/jcm10010042.

Key clinical point: Biomarkers can predict relapse in patients with chronic myeloid leukemia (CML) who are eligible for a controlled treatment interruption.

Major finding: Predictors of CML relapse after treatment interruptions were low levels of cytotoxic cells such as CD56+ with low expression of CD16 and CD94/NKG2 receptors and CD8± T cells expressing TCRγβ+; low expression of activating receptors on the surface of natural killer (NK) and NK T cells; impaired synthesis of proinflammatory cytokines or proteases from NK cells; and HLA-E*0103 homozygosis and KIR haplotype BX.

Study details: The data come from an observational, cross-sectional study of 93 patients with chronic phase CML and 20 age- and gender-matched controls. Among patients with CML, 45 were on treatment with tyrosine kinase inhibitors (TKIs), 27 on sustained treatment-free remission (off TKIs), 15 had a relapse, and 6 had newly diagnosed CML.

Disclosures: The study was funded by the Foundation for Biomedical Research of the Hospital Universitario Ramón y Cajal, the Spanish Ministry of Economy and Competitiveness, and the Spanish AIDS Research Network. The authors declared no conflicts of interest.

Source: Vigón L et al. J Clin Med. 2020 Dec 25. doi: 10.3390/jcm10010042.

Key clinical point: Older age and imatinib therapy were associated with a higher mortality rate in patients with chronic myeloid leukemia (CML) who contracted COVID-19. However, imatinib could be a confounding factor.

Major finding: Outcome was favorable and fatal in 86% and 14% of patients, respectively. COVID-19 mortality rate was higher in patients aged 75 years vs. less than 75 years (60% vs. 7%; P less than .001) and in those on imatinib vs. second-generation tyrosine kinase inhibitors (TKIs) vs. no TKIs (25% vs. 3% vs. 0%; P = .003). However, 25% vs. 0% of patients treated with imatinib vs. second-generation TKIs were more than 75 years old.

Study details: The CANDID study evaluated 110 cases of COVID-19 in patients with CML reported by physicians to the International CML Foundation until July 1, 2020 across 20 countries.

Disclosures: No study sponsor was identified. The lead author reported ties with BMS, Incyte, Novartis, and Pfizer. Some co-authors also reported ties with various pharmaceutical companies.

Source: Rea D et al. ASH 2020. 2020 Dec 7.  Abstract 649.

Key clinical point: Older age and imatinib therapy were associated with a higher mortality rate in patients with chronic myeloid leukemia (CML) who contracted COVID-19. However, imatinib could be a confounding factor.

Major finding: Outcome was favorable and fatal in 86% and 14% of patients, respectively. COVID-19 mortality rate was higher in patients aged 75 years vs. less than 75 years (60% vs. 7%; P less than .001) and in those on imatinib vs. second-generation tyrosine kinase inhibitors (TKIs) vs. no TKIs (25% vs. 3% vs. 0%; P = .003). However, 25% vs. 0% of patients treated with imatinib vs. second-generation TKIs were more than 75 years old.

Study details: The CANDID study evaluated 110 cases of COVID-19 in patients with CML reported by physicians to the International CML Foundation until July 1, 2020 across 20 countries.

Disclosures: No study sponsor was identified. The lead author reported ties with BMS, Incyte, Novartis, and Pfizer. Some co-authors also reported ties with various pharmaceutical companies.

Source: Rea D et al. ASH 2020. 2020 Dec 7.  Abstract 649.

Key clinical point: Older age and imatinib therapy were associated with a higher mortality rate in patients with chronic myeloid leukemia (CML) who contracted COVID-19. However, imatinib could be a confounding factor.

Major finding: Outcome was favorable and fatal in 86% and 14% of patients, respectively. COVID-19 mortality rate was higher in patients aged 75 years vs. less than 75 years (60% vs. 7%; P less than .001) and in those on imatinib vs. second-generation tyrosine kinase inhibitors (TKIs) vs. no TKIs (25% vs. 3% vs. 0%; P = .003). However, 25% vs. 0% of patients treated with imatinib vs. second-generation TKIs were more than 75 years old.

Study details: The CANDID study evaluated 110 cases of COVID-19 in patients with CML reported by physicians to the International CML Foundation until July 1, 2020 across 20 countries.

Disclosures: No study sponsor was identified. The lead author reported ties with BMS, Incyte, Novartis, and Pfizer. Some co-authors also reported ties with various pharmaceutical companies.

Source: Rea D et al. ASH 2020. 2020 Dec 7.  Abstract 649.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.