CML

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.

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