CML

Key clinical point: Creatine kinase (CK) elevation was associated with superior survival in patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) receiving first-line tyrosine kinase inhibitor (TKI) therapies.

Major finding: Overall, 71.7% patients had CK elevation after TKI initiation. Patients with vs. without elevated CK levels had improved overall survival (adjusted hazard ratio [aHR] 0.31; P < .001) and event-free survival (aHR 0.51; P = .003).

Study details: This retrospective study included 283 patients with newly diagnosed CML-CP treated with first-line TKI therapies.

Disclosures: No source of funding was identified. A Bankar reported consulting for Novartis and Celgene. JH Lipton reported consulting for and research funding from Novartis, BMS, Pfizer, and Takeda.

Source: Bankar A et al. Leuk Lymphoma. 2021 Sep 8.doi: 10.1080/10428194.2021.1971219.

Key clinical point: Creatine kinase (CK) elevation was associated with superior survival in patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) receiving first-line tyrosine kinase inhibitor (TKI) therapies.

Major finding: Overall, 71.7% patients had CK elevation after TKI initiation. Patients with vs. without elevated CK levels had improved overall survival (adjusted hazard ratio [aHR] 0.31; P < .001) and event-free survival (aHR 0.51; P = .003).

Study details: This retrospective study included 283 patients with newly diagnosed CML-CP treated with first-line TKI therapies.

Disclosures: No source of funding was identified. A Bankar reported consulting for Novartis and Celgene. JH Lipton reported consulting for and research funding from Novartis, BMS, Pfizer, and Takeda.

Source: Bankar A et al. Leuk Lymphoma. 2021 Sep 8.doi: 10.1080/10428194.2021.1971219.

Key clinical point: Creatine kinase (CK) elevation was associated with superior survival in patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) receiving first-line tyrosine kinase inhibitor (TKI) therapies.

Major finding: Overall, 71.7% patients had CK elevation after TKI initiation. Patients with vs. without elevated CK levels had improved overall survival (adjusted hazard ratio [aHR] 0.31; P < .001) and event-free survival (aHR 0.51; P = .003).

Study details: This retrospective study included 283 patients with newly diagnosed CML-CP treated with first-line TKI therapies.

Disclosures: No source of funding was identified. A Bankar reported consulting for Novartis and Celgene. JH Lipton reported consulting for and research funding from Novartis, BMS, Pfizer, and Takeda.

Source: Bankar A et al. Leuk Lymphoma. 2021 Sep 8.doi: 10.1080/10428194.2021.1971219.

Key clinical point: Advanced age, cough as presenting symptom, imatinib treatment, and cardiovascular comorbidities were associated with mortality due to COVID-19 among patients with chronic myeloid leukemia (CML).

Major finding: The incidence of SARS-CoV-2 infection was 2.5%. The mortality rate was 5.5% among SARS-CoV-2-positive patients and 0.13% in the total cohort of 8,665 CML patients. Predisposing factors among patients who died due to COVID-19 vs. those who remained alive were age > 65 years (83% vs. 70%; P = .03), cough as presenting symptom (50% vs. 28%; P = .001), imatinib therapy (92% vs. 46%; P = .02), and concomitant cardiovascular disorders (50% vs. 13%; P = .001).

Study details: This retrospective study included 8,665 patients with CML followed at 46 centers in Italy between February 2020 and January 2021.

Disclosures: No source of funding or disclosures were reported.

Source: Breccia M et al. Br J Haematol. 2021 Oct 11. doi: 10.1111/bjh.17890.

Key clinical point: Advanced age, cough as presenting symptom, imatinib treatment, and cardiovascular comorbidities were associated with mortality due to COVID-19 among patients with chronic myeloid leukemia (CML).

Major finding: The incidence of SARS-CoV-2 infection was 2.5%. The mortality rate was 5.5% among SARS-CoV-2-positive patients and 0.13% in the total cohort of 8,665 CML patients. Predisposing factors among patients who died due to COVID-19 vs. those who remained alive were age > 65 years (83% vs. 70%; P = .03), cough as presenting symptom (50% vs. 28%; P = .001), imatinib therapy (92% vs. 46%; P = .02), and concomitant cardiovascular disorders (50% vs. 13%; P = .001).

Study details: This retrospective study included 8,665 patients with CML followed at 46 centers in Italy between February 2020 and January 2021.

Disclosures: No source of funding or disclosures were reported.

Source: Breccia M et al. Br J Haematol. 2021 Oct 11. doi: 10.1111/bjh.17890.

Key clinical point: Advanced age, cough as presenting symptom, imatinib treatment, and cardiovascular comorbidities were associated with mortality due to COVID-19 among patients with chronic myeloid leukemia (CML).

Major finding: The incidence of SARS-CoV-2 infection was 2.5%. The mortality rate was 5.5% among SARS-CoV-2-positive patients and 0.13% in the total cohort of 8,665 CML patients. Predisposing factors among patients who died due to COVID-19 vs. those who remained alive were age > 65 years (83% vs. 70%; P = .03), cough as presenting symptom (50% vs. 28%; P = .001), imatinib therapy (92% vs. 46%; P = .02), and concomitant cardiovascular disorders (50% vs. 13%; P = .001).

Study details: This retrospective study included 8,665 patients with CML followed at 46 centers in Italy between February 2020 and January 2021.

Disclosures: No source of funding or disclosures were reported.

Source: Breccia M et al. Br J Haematol. 2021 Oct 11. doi: 10.1111/bjh.17890.

Ponatinib is most likely the most powerful tyrosine kinase inhibitor (TKI) approved for the relapsed or refractory chronic myeloid leukemia (CML) after two lines of therapy. In the original PACE study, ponatinib showed deep and durable responses, but arterial occlusive events (AOE) emerged as notable adverse events. Post hoc analyses indicated that AOEs were dose dependent and recommendations to lower the dose from 45 mg to 30 mg after achieving complete cytogenic response (CCR) and to 15 mg after achieving major molecular response (MMR) were used in an attempt to minimize the cardiovascular toxicities. The question remained regarding the optimal dose of ponatinib in terms of efficacy and toxicity. Cortes et al (Blood 2021 Aug 18.) reported the results of the OPTIC trial where patients with chronic phase CML (CP-CML), resistant/intolerant to at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1T315I mutation, were randomized 1:1:1 to receive 3 different doses of ponatinib daily (45, 30, or 15 mg). Patients who received 45 mg or 30 mg daily reduced their dose to 15 mg upon achievement of response (BCR-ABL1^IS transcript levels ≤1%). The primary endpoint (BCR-ABL1^IS transcript levels ≤1%) was achieved at 12 months in 44.1%, 29.0%, and 23.1% in the 3 cohorts, respectively. Independently confirmed grade 3/4 treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 3 cohorts, respectively. In conclusion, the optimal benefit:risk outcomes occurred with the 45 mg starting dose reduced to 15 mg upon achievement of response.

New drugs with alternative mechanisms of action are always welcome for the treatment of resistant or intolerant CP-CML. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with the potential to overcome resistance or intolerance to approved TKIs. Rea et al (Blood 2021 Aug 18) reported the results of the ASCEMBL trial that compare 40 mg twice daily asciminib vs. bosutinib in patients with CP-CML refractory to >2 previous lines of therapy. The rates of MMR at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). The bosutinib arm, compared to the asciminib arm, had a more frequent occurrence of grade 3 or higher adverse events (AE; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%). This will be another important alternative for CP-CML patients failing 2 lines of therapy; however, it is still unclear if the drug may be superior to ponatinib in the same setting.

In the new era of COVID-19, patients with hematologic malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and an adverse outcome. However, is unclear if this can be seen across the board in all type of hematologic malignancies, as a low mortality rate has been described in patients with CP-CML, suggesting that TKIs may have a protective role against severe COVID-19. Bonifacio et al (Cancer Med 2021 Aug 31) conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in 5 hematologic centers representative of 3 Italian regions. Interestingly, the serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population. The data confirm mild SARS-CoV-2 infection in patients with CML and suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2 similar to the general population.

Ponatinib is most likely the most powerful tyrosine kinase inhibitor (TKI) approved for the relapsed or refractory chronic myeloid leukemia (CML) after two lines of therapy. In the original PACE study, ponatinib showed deep and durable responses, but arterial occlusive events (AOE) emerged as notable adverse events. Post hoc analyses indicated that AOEs were dose dependent and recommendations to lower the dose from 45 mg to 30 mg after achieving complete cytogenic response (CCR) and to 15 mg after achieving major molecular response (MMR) were used in an attempt to minimize the cardiovascular toxicities. The question remained regarding the optimal dose of ponatinib in terms of efficacy and toxicity. Cortes et al (Blood 2021 Aug 18.) reported the results of the OPTIC trial where patients with chronic phase CML (CP-CML), resistant/intolerant to at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1T315I mutation, were randomized 1:1:1 to receive 3 different doses of ponatinib daily (45, 30, or 15 mg). Patients who received 45 mg or 30 mg daily reduced their dose to 15 mg upon achievement of response (BCR-ABL1^IS transcript levels ≤1%). The primary endpoint (BCR-ABL1^IS transcript levels ≤1%) was achieved at 12 months in 44.1%, 29.0%, and 23.1% in the 3 cohorts, respectively. Independently confirmed grade 3/4 treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 3 cohorts, respectively. In conclusion, the optimal benefit:risk outcomes occurred with the 45 mg starting dose reduced to 15 mg upon achievement of response.

New drugs with alternative mechanisms of action are always welcome for the treatment of resistant or intolerant CP-CML. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with the potential to overcome resistance or intolerance to approved TKIs. Rea et al (Blood 2021 Aug 18) reported the results of the ASCEMBL trial that compare 40 mg twice daily asciminib vs. bosutinib in patients with CP-CML refractory to >2 previous lines of therapy. The rates of MMR at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). The bosutinib arm, compared to the asciminib arm, had a more frequent occurrence of grade 3 or higher adverse events (AE; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%). This will be another important alternative for CP-CML patients failing 2 lines of therapy; however, it is still unclear if the drug may be superior to ponatinib in the same setting.

In the new era of COVID-19, patients with hematologic malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and an adverse outcome. However, is unclear if this can be seen across the board in all type of hematologic malignancies, as a low mortality rate has been described in patients with CP-CML, suggesting that TKIs may have a protective role against severe COVID-19. Bonifacio et al (Cancer Med 2021 Aug 31) conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in 5 hematologic centers representative of 3 Italian regions. Interestingly, the serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population. The data confirm mild SARS-CoV-2 infection in patients with CML and suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2 similar to the general population.

Ponatinib is most likely the most powerful tyrosine kinase inhibitor (TKI) approved for the relapsed or refractory chronic myeloid leukemia (CML) after two lines of therapy. In the original PACE study, ponatinib showed deep and durable responses, but arterial occlusive events (AOE) emerged as notable adverse events. Post hoc analyses indicated that AOEs were dose dependent and recommendations to lower the dose from 45 mg to 30 mg after achieving complete cytogenic response (CCR) and to 15 mg after achieving major molecular response (MMR) were used in an attempt to minimize the cardiovascular toxicities. The question remained regarding the optimal dose of ponatinib in terms of efficacy and toxicity. Cortes et al (Blood 2021 Aug 18.) reported the results of the OPTIC trial where patients with chronic phase CML (CP-CML), resistant/intolerant to at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1T315I mutation, were randomized 1:1:1 to receive 3 different doses of ponatinib daily (45, 30, or 15 mg). Patients who received 45 mg or 30 mg daily reduced their dose to 15 mg upon achievement of response (BCR-ABL1^IS transcript levels ≤1%). The primary endpoint (BCR-ABL1^IS transcript levels ≤1%) was achieved at 12 months in 44.1%, 29.0%, and 23.1% in the 3 cohorts, respectively. Independently confirmed grade 3/4 treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 3 cohorts, respectively. In conclusion, the optimal benefit:risk outcomes occurred with the 45 mg starting dose reduced to 15 mg upon achievement of response.

New drugs with alternative mechanisms of action are always welcome for the treatment of resistant or intolerant CP-CML. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with the potential to overcome resistance or intolerance to approved TKIs. Rea et al (Blood 2021 Aug 18) reported the results of the ASCEMBL trial that compare 40 mg twice daily asciminib vs. bosutinib in patients with CP-CML refractory to >2 previous lines of therapy. The rates of MMR at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). The bosutinib arm, compared to the asciminib arm, had a more frequent occurrence of grade 3 or higher adverse events (AE; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%). This will be another important alternative for CP-CML patients failing 2 lines of therapy; however, it is still unclear if the drug may be superior to ponatinib in the same setting.

In the new era of COVID-19, patients with hematologic malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and an adverse outcome. However, is unclear if this can be seen across the board in all type of hematologic malignancies, as a low mortality rate has been described in patients with CP-CML, suggesting that TKIs may have a protective role against severe COVID-19. Bonifacio et al (Cancer Med 2021 Aug 31) conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in 5 hematologic centers representative of 3 Italian regions. Interestingly, the serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population. The data confirm mild SARS-CoV-2 infection in patients with CML and suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2 similar to the general population.

Key clinical point: Prevalence of positive anti-SARS-CoV-2 antibodies was similar in chronic myeloid leukemia (CML) population and general populations in Italy and was not associated with the type of tyrosine kinase inhibitor (TKI) therapy or treatment-free remission (TFR) status, thereby reassuring the safe continuation of TKI treatment in patients with CML during the COVID-19 pandemic.

Major finding: The prevalence of SARS-CoV-2 infection was comparable in CML (1.95%; 95% CI 1.09-3.46) and general (2.5%) populations in Italy. Positive anti-SARS-CoV-2 serological test was not associated with the type of TKI treatment (P = .19) or TFR status (P = .40).

Study details: Findings are from a cross-sectional study including 564 adult patients with CML tested for anti-SARS-CoV-2 immunoglobulin (Ig)M and/or IgG antibodies.

Disclosures: This study was supported by Fondazione Cariverona (ENACT Project). The authors declared no conflict of interests.

Source: Bonifacio M et al. Cancer Med. 2021 Aug 31. doi: 10.1002/cam4.4179.

Key clinical point: Prevalence of positive anti-SARS-CoV-2 antibodies was similar in chronic myeloid leukemia (CML) population and general populations in Italy and was not associated with the type of tyrosine kinase inhibitor (TKI) therapy or treatment-free remission (TFR) status, thereby reassuring the safe continuation of TKI treatment in patients with CML during the COVID-19 pandemic.

Major finding: The prevalence of SARS-CoV-2 infection was comparable in CML (1.95%; 95% CI 1.09-3.46) and general (2.5%) populations in Italy. Positive anti-SARS-CoV-2 serological test was not associated with the type of TKI treatment (P = .19) or TFR status (P = .40).

Study details: Findings are from a cross-sectional study including 564 adult patients with CML tested for anti-SARS-CoV-2 immunoglobulin (Ig)M and/or IgG antibodies.

Disclosures: This study was supported by Fondazione Cariverona (ENACT Project). The authors declared no conflict of interests.

Source: Bonifacio M et al. Cancer Med. 2021 Aug 31. doi: 10.1002/cam4.4179.

Key clinical point: Prevalence of positive anti-SARS-CoV-2 antibodies was similar in chronic myeloid leukemia (CML) population and general populations in Italy and was not associated with the type of tyrosine kinase inhibitor (TKI) therapy or treatment-free remission (TFR) status, thereby reassuring the safe continuation of TKI treatment in patients with CML during the COVID-19 pandemic.

Major finding: The prevalence of SARS-CoV-2 infection was comparable in CML (1.95%; 95% CI 1.09-3.46) and general (2.5%) populations in Italy. Positive anti-SARS-CoV-2 serological test was not associated with the type of TKI treatment (P = .19) or TFR status (P = .40).

Study details: Findings are from a cross-sectional study including 564 adult patients with CML tested for anti-SARS-CoV-2 immunoglobulin (Ig)M and/or IgG antibodies.

Disclosures: This study was supported by Fondazione Cariverona (ENACT Project). The authors declared no conflict of interests.

Source: Bonifacio M et al. Cancer Med. 2021 Aug 31. doi: 10.1002/cam4.4179.

Key clinical point: Imatinib discontinuation was feasible without affecting clinical outcomes in pediatric patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with frontline imatinib with a sustained deep molecular response (DMR) for at least 2 years with imatinib.

Major finding: The molecular-free remission rate at 6, 12, and 36 months was 61%, 56%, and 56%, respectively. Of the 7 children who had a molecular relapse, 6 regained molecular response (MR) 4 and 1 patient achieved major MR after restarting imatinib. No deaths or disease progression were reported.

Study details: Findings are from a retrospective analysis of 18 children with CML-CP from the International Registry of Childhood CML who were treated with frontline imatinib and had sustained MR4 for at least 2 years before imatinib discontinuation to attempt treatment-free remission.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Millot F et al. Cancers. 2021 Aug 15. doi: 10.3390/cancers13164102.

Key clinical point: Imatinib discontinuation was feasible without affecting clinical outcomes in pediatric patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with frontline imatinib with a sustained deep molecular response (DMR) for at least 2 years with imatinib.

Major finding: The molecular-free remission rate at 6, 12, and 36 months was 61%, 56%, and 56%, respectively. Of the 7 children who had a molecular relapse, 6 regained molecular response (MR) 4 and 1 patient achieved major MR after restarting imatinib. No deaths or disease progression were reported.

Study details: Findings are from a retrospective analysis of 18 children with CML-CP from the International Registry of Childhood CML who were treated with frontline imatinib and had sustained MR4 for at least 2 years before imatinib discontinuation to attempt treatment-free remission.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Millot F et al. Cancers. 2021 Aug 15. doi: 10.3390/cancers13164102.

Key clinical point: Imatinib discontinuation was feasible without affecting clinical outcomes in pediatric patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with frontline imatinib with a sustained deep molecular response (DMR) for at least 2 years with imatinib.

Major finding: The molecular-free remission rate at 6, 12, and 36 months was 61%, 56%, and 56%, respectively. Of the 7 children who had a molecular relapse, 6 regained molecular response (MR) 4 and 1 patient achieved major MR after restarting imatinib. No deaths or disease progression were reported.

Study details: Findings are from a retrospective analysis of 18 children with CML-CP from the International Registry of Childhood CML who were treated with frontline imatinib and had sustained MR4 for at least 2 years before imatinib discontinuation to attempt treatment-free remission.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Millot F et al. Cancers. 2021 Aug 15. doi: 10.3390/cancers13164102.

Key clinical point: Improvements in patient-reported functional outcomes in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) deteriorated after restarting tyrosine kinase inhibitor (TKI).

Major finding: Among patients in TFR at 12 months, 92.0% had at least a 3-point improvement in social function, 71.4% in social isolation, 9.8% in sexual satisfaction, and 3.6% in physical function. No patients had at least a 3-point improvement in cognitive function or interest in sexual activity. All functional changes worsened after restarting TKI.

Study details: Findings are from the prospective LAST study including 172 adult patients with CML-CP attempting TFR after at least 3 years of treatment with a first- or second-generation TKI and at least 2 years in molecular response 4.

Disclosures: This study was supported by the National Cancer Institute at the National Institute of Health. The lead author reported research support from the American Society of Hematology. Some investigators reported ties with various pharmaceutical companies.

Source: Schoenbeck KL et al. J Natl Cancer Inst. 2021 Sep 7. doi: 10.1093/jnci/djab184.

Key clinical point: Improvements in patient-reported functional outcomes in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) deteriorated after restarting tyrosine kinase inhibitor (TKI).

Major finding: Among patients in TFR at 12 months, 92.0% had at least a 3-point improvement in social function, 71.4% in social isolation, 9.8% in sexual satisfaction, and 3.6% in physical function. No patients had at least a 3-point improvement in cognitive function or interest in sexual activity. All functional changes worsened after restarting TKI.

Study details: Findings are from the prospective LAST study including 172 adult patients with CML-CP attempting TFR after at least 3 years of treatment with a first- or second-generation TKI and at least 2 years in molecular response 4.

Disclosures: This study was supported by the National Cancer Institute at the National Institute of Health. The lead author reported research support from the American Society of Hematology. Some investigators reported ties with various pharmaceutical companies.

Source: Schoenbeck KL et al. J Natl Cancer Inst. 2021 Sep 7. doi: 10.1093/jnci/djab184.

Key clinical point: Improvements in patient-reported functional outcomes in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) deteriorated after restarting tyrosine kinase inhibitor (TKI).

Major finding: Among patients in TFR at 12 months, 92.0% had at least a 3-point improvement in social function, 71.4% in social isolation, 9.8% in sexual satisfaction, and 3.6% in physical function. No patients had at least a 3-point improvement in cognitive function or interest in sexual activity. All functional changes worsened after restarting TKI.

Study details: Findings are from the prospective LAST study including 172 adult patients with CML-CP attempting TFR after at least 3 years of treatment with a first- or second-generation TKI and at least 2 years in molecular response 4.

Disclosures: This study was supported by the National Cancer Institute at the National Institute of Health. The lead author reported research support from the American Society of Hematology. Some investigators reported ties with various pharmaceutical companies.

Source: Schoenbeck KL et al. J Natl Cancer Inst. 2021 Sep 7. doi: 10.1093/jnci/djab184.

Key clinical point: BCR-ABL1 transcript doubling time (DT) at 2 months was strongly associated with treatment-free remission (TFR) failure after imatinib discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The molecular recurrence-free survival at 12 months was 5.0% in patients in the high-risk (DT at 2 months, <12.75 days) vs. 47.2% in the intermediate-risk (DT at 2 months, ≥12.75 days) and 90.1% in the low-risk (DT at 2 months, 0 or less) groups (P < .001). DT at 2 months determined high-risk (hazard ratio [HR] 8.062; P = .0006) and low-risk (HR 0.196; P = .0110) groups for TFR failure.

Study details: This study assessed 131 patients with CML-CP in the imatinib discontinuation phase enrolled in the TRAD study.

Disclosures: This study was supported by BMS Canada and partly by the Princess Margaret Cancer Foundation. The lead author reported a research grant from the BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Sep 8. doi: 10.1111/bjh.17807

Key clinical point: BCR-ABL1 transcript doubling time (DT) at 2 months was strongly associated with treatment-free remission (TFR) failure after imatinib discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The molecular recurrence-free survival at 12 months was 5.0% in patients in the high-risk (DT at 2 months, <12.75 days) vs. 47.2% in the intermediate-risk (DT at 2 months, ≥12.75 days) and 90.1% in the low-risk (DT at 2 months, 0 or less) groups (P < .001). DT at 2 months determined high-risk (hazard ratio [HR] 8.062; P = .0006) and low-risk (HR 0.196; P = .0110) groups for TFR failure.

Study details: This study assessed 131 patients with CML-CP in the imatinib discontinuation phase enrolled in the TRAD study.

Disclosures: This study was supported by BMS Canada and partly by the Princess Margaret Cancer Foundation. The lead author reported a research grant from the BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Sep 8. doi: 10.1111/bjh.17807

Key clinical point: BCR-ABL1 transcript doubling time (DT) at 2 months was strongly associated with treatment-free remission (TFR) failure after imatinib discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The molecular recurrence-free survival at 12 months was 5.0% in patients in the high-risk (DT at 2 months, <12.75 days) vs. 47.2% in the intermediate-risk (DT at 2 months, ≥12.75 days) and 90.1% in the low-risk (DT at 2 months, 0 or less) groups (P < .001). DT at 2 months determined high-risk (hazard ratio [HR] 8.062; P = .0006) and low-risk (HR 0.196; P = .0110) groups for TFR failure.

Study details: This study assessed 131 patients with CML-CP in the imatinib discontinuation phase enrolled in the TRAD study.

Disclosures: This study was supported by BMS Canada and partly by the Princess Margaret Cancer Foundation. The lead author reported a research grant from the BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Sep 8. doi: 10.1111/bjh.17807

Key clinical point: Asciminib showed superior efficacy and a favorable safety profile compared with bosutinib in patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant or intolerant to at least 2 prior tyrosine kinase inhibitor (TKI) therapies.

Major finding: The rates of major molecular response (MMR) at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). Bosutinib vs. asciminib arms had a more frequent occurrence of grade 3 or higher adverse events (AEs; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%).

Study details: Findings are from the phase 3 ASCEMBL trial including 233 adult patients with CML-CP previously treated with at least 2 TKIs randomly assigned to receive either 40 mg asciminib twice daily or 500 mg bosutinib once daily.

Disclosures: This study was sponsored and funded by Novartis Pharmaceuticals Corporation. Some investigators including, the lead author, reported ties with various pharmaceutical companies, including Novartis.

Source: Rea D et al. Blood. 2021 Aug 18. doi: 10.1182/blood.2020009984.

Key clinical point: Asciminib showed superior efficacy and a favorable safety profile compared with bosutinib in patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant or intolerant to at least 2 prior tyrosine kinase inhibitor (TKI) therapies.

Major finding: The rates of major molecular response (MMR) at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). Bosutinib vs. asciminib arms had a more frequent occurrence of grade 3 or higher adverse events (AEs; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%).

Study details: Findings are from the phase 3 ASCEMBL trial including 233 adult patients with CML-CP previously treated with at least 2 TKIs randomly assigned to receive either 40 mg asciminib twice daily or 500 mg bosutinib once daily.

Disclosures: This study was sponsored and funded by Novartis Pharmaceuticals Corporation. Some investigators including, the lead author, reported ties with various pharmaceutical companies, including Novartis.

Source: Rea D et al. Blood. 2021 Aug 18. doi: 10.1182/blood.2020009984.

Key clinical point: Asciminib showed superior efficacy and a favorable safety profile compared with bosutinib in patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant or intolerant to at least 2 prior tyrosine kinase inhibitor (TKI) therapies.

Major finding: The rates of major molecular response (MMR) at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). Bosutinib vs. asciminib arms had a more frequent occurrence of grade 3 or higher adverse events (AEs; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%).

Study details: Findings are from the phase 3 ASCEMBL trial including 233 adult patients with CML-CP previously treated with at least 2 TKIs randomly assigned to receive either 40 mg asciminib twice daily or 500 mg bosutinib once daily.

Disclosures: This study was sponsored and funded by Novartis Pharmaceuticals Corporation. Some investigators including, the lead author, reported ties with various pharmaceutical companies, including Novartis.

Source: Rea D et al. Blood. 2021 Aug 18. doi: 10.1182/blood.2020009984.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP) undergoing tyrosine kinase inhibitor (TKI) treatment, the European Treatment and Outcome Study for CML long-term survival (ELTS) offered better overall prediction accuracy than the Sokal score, especially in those receiving the second-generation TKI (2G-TKIs).

Major finding: Overall, ELTS was a better predictor of molecular response (MR)4 (high vs. low; hazard ratio [HR], 0.6; P = .013), MR4.5 (high vs. low; HR, 0.6; P = .030), and CML-related survival (high vs. low; HR, 4.3; P < .001) than the Sokal score. In patients receiving 2G-TKIs, only the ELTS score predicted complete cytogenic response, major MR, MR4, and failure- and progression-free survival (all P < .05).

Study details: Findings are from a retrospective analysis of 1,661 adult patients with newly

diagnosed CML-CP receiving either imatinib, dasatinib, or nilotinib.

Disclosures: This study was partly funded by the National Nature Science Foundation of China. RP

Gale reported ties with various pharmaceutical companies. Other authors had no disclosures.

Source: Zhang XS et al. Leukemia. 2021 Aug 19. doi: 10.1038/s41375-021-01387-y.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP) undergoing tyrosine kinase inhibitor (TKI) treatment, the European Treatment and Outcome Study for CML long-term survival (ELTS) offered better overall prediction accuracy than the Sokal score, especially in those receiving the second-generation TKI (2G-TKIs).

Major finding: Overall, ELTS was a better predictor of molecular response (MR)4 (high vs. low; hazard ratio [HR], 0.6; P = .013), MR4.5 (high vs. low; HR, 0.6; P = .030), and CML-related survival (high vs. low; HR, 4.3; P < .001) than the Sokal score. In patients receiving 2G-TKIs, only the ELTS score predicted complete cytogenic response, major MR, MR4, and failure- and progression-free survival (all P < .05).

Study details: Findings are from a retrospective analysis of 1,661 adult patients with newly

diagnosed CML-CP receiving either imatinib, dasatinib, or nilotinib.

Disclosures: This study was partly funded by the National Nature Science Foundation of China. RP

Gale reported ties with various pharmaceutical companies. Other authors had no disclosures.

Source: Zhang XS et al. Leukemia. 2021 Aug 19. doi: 10.1038/s41375-021-01387-y.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP) undergoing tyrosine kinase inhibitor (TKI) treatment, the European Treatment and Outcome Study for CML long-term survival (ELTS) offered better overall prediction accuracy than the Sokal score, especially in those receiving the second-generation TKI (2G-TKIs).

Major finding: Overall, ELTS was a better predictor of molecular response (MR)4 (high vs. low; hazard ratio [HR], 0.6; P = .013), MR4.5 (high vs. low; HR, 0.6; P = .030), and CML-related survival (high vs. low; HR, 4.3; P < .001) than the Sokal score. In patients receiving 2G-TKIs, only the ELTS score predicted complete cytogenic response, major MR, MR4, and failure- and progression-free survival (all P < .05).

Study details: Findings are from a retrospective analysis of 1,661 adult patients with newly

diagnosed CML-CP receiving either imatinib, dasatinib, or nilotinib.

Disclosures: This study was partly funded by the National Nature Science Foundation of China. RP

Gale reported ties with various pharmaceutical companies. Other authors had no disclosures.

Source: Zhang XS et al. Leukemia. 2021 Aug 19. doi: 10.1038/s41375-021-01387-y.

Key clinical point: Pulmonary hypertension (PH) is common in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI), warranting careful screening for PH in this patient population.

Major finding: Overall, 10.7% of patients undergoing transthoracic echocardiography (TTE) during TKI treatment were diagnosed with PH. Dasatinib treatment (odds ratio [OR] 8.2; P = .03), age above 60 years (OR 12.3; P = .04), and presence of cardiopulmonary symptoms/signs (OR 36.1; P = .001) were significant risk factors for PH.

Study details: Findings are from a retrospective analysis of 112 patients with CML who underwent TTE during TKI treatment.

Disclosures: This study was funded by the Research Fund of Chungnam National University Hospital and the Bio and Medical Technology Development Program of the National Research Foundation of Korea. The authors declared no conflict of interests.

Source: Song IC et al. Medicine. 2021 Aug 20. doi: 10.1097/MD.0000000000026975.

Key clinical point: Pulmonary hypertension (PH) is common in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI), warranting careful screening for PH in this patient population.

Major finding: Overall, 10.7% of patients undergoing transthoracic echocardiography (TTE) during TKI treatment were diagnosed with PH. Dasatinib treatment (odds ratio [OR] 8.2; P = .03), age above 60 years (OR 12.3; P = .04), and presence of cardiopulmonary symptoms/signs (OR 36.1; P = .001) were significant risk factors for PH.

Study details: Findings are from a retrospective analysis of 112 patients with CML who underwent TTE during TKI treatment.

Disclosures: This study was funded by the Research Fund of Chungnam National University Hospital and the Bio and Medical Technology Development Program of the National Research Foundation of Korea. The authors declared no conflict of interests.

Source: Song IC et al. Medicine. 2021 Aug 20. doi: 10.1097/MD.0000000000026975.

Key clinical point: Pulmonary hypertension (PH) is common in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI), warranting careful screening for PH in this patient population.

Major finding: Overall, 10.7% of patients undergoing transthoracic echocardiography (TTE) during TKI treatment were diagnosed with PH. Dasatinib treatment (odds ratio [OR] 8.2; P = .03), age above 60 years (OR 12.3; P = .04), and presence of cardiopulmonary symptoms/signs (OR 36.1; P = .001) were significant risk factors for PH.

Study details: Findings are from a retrospective analysis of 112 patients with CML who underwent TTE during TKI treatment.

Disclosures: This study was funded by the Research Fund of Chungnam National University Hospital and the Bio and Medical Technology Development Program of the National Research Foundation of Korea. The authors declared no conflict of interests.

Source: Song IC et al. Medicine. 2021 Aug 20. doi: 10.1097/MD.0000000000026975.