CML

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.

Key clinical point: The addition of low-dose pegylated interferon-a2b (PegIFN-a2b) to dasatinib 3 months after initiation of tyrosine kinase inhibitor was effective and well tolerated without an increased risk for late toxicity in patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 5 years, rates of major molecular response (MR), MR4, and MR4.5 were 84.6%, 64.1%, and 51.3%, respectively. No disease progression or CML-related deaths were observed. Grade 2 or higher hematological adverse events were not observed after 12 months. After 24 months, pleural effusion was reported in 10% of patients.

Study details: Findings are from a 5-year follow-up of phase 2 NordCML007 trial including 40 adult patients with newly diagnosed CML-CP who were given upfront dasatinib. Low-dose PegIFN-a2b was added from months 4 to 15 after dasatinib initiation.

Disclosures: This study was sponsored by the Norwegian University of Science and Technology. No disclosures were reported.

Source: Flygt H et al. Eur J Haematol. 2021 Aug 21. doi: 10.1111/ejh.13699.

Key clinical point: The addition of low-dose pegylated interferon-a2b (PegIFN-a2b) to dasatinib 3 months after initiation of tyrosine kinase inhibitor was effective and well tolerated without an increased risk for late toxicity in patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 5 years, rates of major molecular response (MR), MR4, and MR4.5 were 84.6%, 64.1%, and 51.3%, respectively. No disease progression or CML-related deaths were observed. Grade 2 or higher hematological adverse events were not observed after 12 months. After 24 months, pleural effusion was reported in 10% of patients.

Study details: Findings are from a 5-year follow-up of phase 2 NordCML007 trial including 40 adult patients with newly diagnosed CML-CP who were given upfront dasatinib. Low-dose PegIFN-a2b was added from months 4 to 15 after dasatinib initiation.

Disclosures: This study was sponsored by the Norwegian University of Science and Technology. No disclosures were reported.

Source: Flygt H et al. Eur J Haematol. 2021 Aug 21. doi: 10.1111/ejh.13699.

Key clinical point: The addition of low-dose pegylated interferon-a2b (PegIFN-a2b) to dasatinib 3 months after initiation of tyrosine kinase inhibitor was effective and well tolerated without an increased risk for late toxicity in patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 5 years, rates of major molecular response (MR), MR4, and MR4.5 were 84.6%, 64.1%, and 51.3%, respectively. No disease progression or CML-related deaths were observed. Grade 2 or higher hematological adverse events were not observed after 12 months. After 24 months, pleural effusion was reported in 10% of patients.

Study details: Findings are from a 5-year follow-up of phase 2 NordCML007 trial including 40 adult patients with newly diagnosed CML-CP who were given upfront dasatinib. Low-dose PegIFN-a2b was added from months 4 to 15 after dasatinib initiation.

Disclosures: This study was sponsored by the Norwegian University of Science and Technology. No disclosures were reported.

Source: Flygt H et al. Eur J Haematol. 2021 Aug 21. doi: 10.1111/ejh.13699.

Key clinical point: Although all starting ponatinib doses showed clinical benefit among patients with resistant chronic-phase chronic myeloid leukemia (CML-CP), the optimal benefit-risk ratio was observed with 45 mg ponatinib reduced to 15 mg on achievement of a response.

Major finding: The response rates at 12 months in patients receiving 45 mg, 30 mg, or 15 mg ponatinib were 44.1% (98.3% CI 31.7%-57.0%), 29.0% (98.3% CI 18.4%-41.6%), and 23.1% (98.3% CI 13.4%-35.3%), respectively. Grade 3-5 treatment-emergent arterial occlusive events were observed in 5, 5, and 3 patients in the 45, 30, and 15 mg ponatinib cohorts, respectively.

Study details: The phase 2 OPTIC trial included 283 adult patients with CML-CP resistant/intolerant to at least 2 prior tyrosine kinase inhibitors or with T315l mutation, randomly assigned to receive a once-daily starting dose of 45 mg, 30 mg, or 15 mg ponatinib. Patients receiving 45 mg or 30 mg doses were reduced to 15 mg upon achievement of a response.

Disclosures: No source of funding was identified other than Millennium Pharmaceuticals, Inc. for medical writing assistance. Some investigators, including the lead author, reported ties with various pharmaceutical companies.

Source: Cortes J et al. Blood. 2021 Aug 18. doi: 10.1182/blood.2021012082.

Key clinical point: Although all starting ponatinib doses showed clinical benefit among patients with resistant chronic-phase chronic myeloid leukemia (CML-CP), the optimal benefit-risk ratio was observed with 45 mg ponatinib reduced to 15 mg on achievement of a response.

Major finding: The response rates at 12 months in patients receiving 45 mg, 30 mg, or 15 mg ponatinib were 44.1% (98.3% CI 31.7%-57.0%), 29.0% (98.3% CI 18.4%-41.6%), and 23.1% (98.3% CI 13.4%-35.3%), respectively. Grade 3-5 treatment-emergent arterial occlusive events were observed in 5, 5, and 3 patients in the 45, 30, and 15 mg ponatinib cohorts, respectively.

Study details: The phase 2 OPTIC trial included 283 adult patients with CML-CP resistant/intolerant to at least 2 prior tyrosine kinase inhibitors or with T315l mutation, randomly assigned to receive a once-daily starting dose of 45 mg, 30 mg, or 15 mg ponatinib. Patients receiving 45 mg or 30 mg doses were reduced to 15 mg upon achievement of a response.

Disclosures: No source of funding was identified other than Millennium Pharmaceuticals, Inc. for medical writing assistance. Some investigators, including the lead author, reported ties with various pharmaceutical companies.

Source: Cortes J et al. Blood. 2021 Aug 18. doi: 10.1182/blood.2021012082.

Key clinical point: Although all starting ponatinib doses showed clinical benefit among patients with resistant chronic-phase chronic myeloid leukemia (CML-CP), the optimal benefit-risk ratio was observed with 45 mg ponatinib reduced to 15 mg on achievement of a response.

Major finding: The response rates at 12 months in patients receiving 45 mg, 30 mg, or 15 mg ponatinib were 44.1% (98.3% CI 31.7%-57.0%), 29.0% (98.3% CI 18.4%-41.6%), and 23.1% (98.3% CI 13.4%-35.3%), respectively. Grade 3-5 treatment-emergent arterial occlusive events were observed in 5, 5, and 3 patients in the 45, 30, and 15 mg ponatinib cohorts, respectively.

Study details: The phase 2 OPTIC trial included 283 adult patients with CML-CP resistant/intolerant to at least 2 prior tyrosine kinase inhibitors or with T315l mutation, randomly assigned to receive a once-daily starting dose of 45 mg, 30 mg, or 15 mg ponatinib. Patients receiving 45 mg or 30 mg doses were reduced to 15 mg upon achievement of a response.

Disclosures: No source of funding was identified other than Millennium Pharmaceuticals, Inc. for medical writing assistance. Some investigators, including the lead author, reported ties with various pharmaceutical companies.

Source: Cortes J et al. Blood. 2021 Aug 18. doi: 10.1182/blood.2021012082.

Key clinical point: Patients with chronic myeloid leukemia (CML) treated with first-line nilotinib vs. imatinib may have a higher risk for vascular adverse events (VAE), suggesting that older patients and those with a history of cerebrovascular diseases using nilotinib should be closely monitored.

Major finding: The risk for VAEs was significantly higher in patients treated with nilotinib vs. imatinib (hazard ratio 3.13; P < .05). Nilotinib use (odds ratio [OR] 3.43; P = .03), older age (OR, 1.04; P < .01), and history of cerebrovascular diseases (OR, 3.49; P = .02) were significant risk factors for VAEs.

Study details: Findings are from a retrospective analysis of 1,111 adult patients with CML treated with either frontline imatinib (n=565), nilotinib (n=306), or dasatinib (n=240).

Disclosures: No funding source or disclosures were reported.

Source: Chen MT et al. Oncologist. 2021 Aug 21. doi: 10.1002/onco.13944.

Key clinical point: Patients with chronic myeloid leukemia (CML) treated with first-line nilotinib vs. imatinib may have a higher risk for vascular adverse events (VAE), suggesting that older patients and those with a history of cerebrovascular diseases using nilotinib should be closely monitored.

Major finding: The risk for VAEs was significantly higher in patients treated with nilotinib vs. imatinib (hazard ratio 3.13; P < .05). Nilotinib use (odds ratio [OR] 3.43; P = .03), older age (OR, 1.04; P < .01), and history of cerebrovascular diseases (OR, 3.49; P = .02) were significant risk factors for VAEs.

Study details: Findings are from a retrospective analysis of 1,111 adult patients with CML treated with either frontline imatinib (n=565), nilotinib (n=306), or dasatinib (n=240).

Disclosures: No funding source or disclosures were reported.

Source: Chen MT et al. Oncologist. 2021 Aug 21. doi: 10.1002/onco.13944.

Key clinical point: Patients with chronic myeloid leukemia (CML) treated with first-line nilotinib vs. imatinib may have a higher risk for vascular adverse events (VAE), suggesting that older patients and those with a history of cerebrovascular diseases using nilotinib should be closely monitored.

Major finding: The risk for VAEs was significantly higher in patients treated with nilotinib vs. imatinib (hazard ratio 3.13; P < .05). Nilotinib use (odds ratio [OR] 3.43; P = .03), older age (OR, 1.04; P < .01), and history of cerebrovascular diseases (OR, 3.49; P = .02) were significant risk factors for VAEs.

Study details: Findings are from a retrospective analysis of 1,111 adult patients with CML treated with either frontline imatinib (n=565), nilotinib (n=306), or dasatinib (n=240).

Disclosures: No funding source or disclosures were reported.

Source: Chen MT et al. Oncologist. 2021 Aug 21. doi: 10.1002/onco.13944.

Latin American countries have a high rate of SARS-CoV-2 infection and some of the highest COVID-19 deaths worldwide. Brazil, Colombia, Argentina, and Mexico have reported the highest number of confirmed cases. More recently has been reported that in series form US and Europe the mortality of COVID-19 has not been as high as reported in other hematological conditions and the response to vaccination also has bene described as high. In a recent report, Pagnano et al. (Leuk Lymphoma. 2021) has recently reported the clinical evolution and outcome of COVID-19 in patients with chronic myeloid leukemia in Latin America. In an observational multicenter study with a total of 92 patients with COVID-19 between March and December 2020 with 26% of whom were severe or critical. Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. Almost half of them had at least one comorbidity. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; P = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates (100 and 89%) than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (50 and 33%).

Currently the most common reason for TKI discontinuation is intolerance. Ma et al (Leuk Res. 2021) reports the long-term outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4–90.6 %). However, amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2–80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Patients who switch for intolerance continue to enjoy excellent long term clinical outcomes.

Latin American countries have a high rate of SARS-CoV-2 infection and some of the highest COVID-19 deaths worldwide. Brazil, Colombia, Argentina, and Mexico have reported the highest number of confirmed cases. More recently has been reported that in series form US and Europe the mortality of COVID-19 has not been as high as reported in other hematological conditions and the response to vaccination also has bene described as high. In a recent report, Pagnano et al. (Leuk Lymphoma. 2021) has recently reported the clinical evolution and outcome of COVID-19 in patients with chronic myeloid leukemia in Latin America. In an observational multicenter study with a total of 92 patients with COVID-19 between March and December 2020 with 26% of whom were severe or critical. Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. Almost half of them had at least one comorbidity. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; P = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates (100 and 89%) than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (50 and 33%).

Currently the most common reason for TKI discontinuation is intolerance. Ma et al (Leuk Res. 2021) reports the long-term outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4–90.6 %). However, amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2–80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Patients who switch for intolerance continue to enjoy excellent long term clinical outcomes.

Latin American countries have a high rate of SARS-CoV-2 infection and some of the highest COVID-19 deaths worldwide. Brazil, Colombia, Argentina, and Mexico have reported the highest number of confirmed cases. More recently has been reported that in series form US and Europe the mortality of COVID-19 has not been as high as reported in other hematological conditions and the response to vaccination also has bene described as high. In a recent report, Pagnano et al. (Leuk Lymphoma. 2021) has recently reported the clinical evolution and outcome of COVID-19 in patients with chronic myeloid leukemia in Latin America. In an observational multicenter study with a total of 92 patients with COVID-19 between March and December 2020 with 26% of whom were severe or critical. Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. Almost half of them had at least one comorbidity. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; P = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates (100 and 89%) than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (50 and 33%).

Currently the most common reason for TKI discontinuation is intolerance. Ma et al (Leuk Res. 2021) reports the long-term outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4–90.6 %). However, amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2–80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Patients who switch for intolerance continue to enjoy excellent long term clinical outcomes.

Key clinical point: Natural killer (NK) cell subsets, particularly CD56bright NK cells, were associated with relapse outcomes after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP). Moreover, interferon-a therapy gradually increased levels of CD56bright NK cells.

Major finding: Among patients who did not receive interferon-a therapy, the nonrelapsed vs relapsed patients had a significantly higher proportion of CD3-CD56+ NK cells (P = .016), particularly CD3-CD56dimCD16+ NK cells (P = .017), at 1 month after TKI discontinuation. Patients who received interferon-a therapy showed an increase in CD56bright NK cells at 3- and 6- months post-therapy vs pre-therapy (P < .05).

Study details: Findings are from a retrospective analysis of 34 patients with CML-CP who discontinued TKI therapy after 3 or more years and at least 2 years of MR4.5. Twelve patients received interferon-a therapy post-TKI discontinuation.

Disclosures: This study was supported by the Capital Characteristic Clinic Project Foundation. The authors declared no conflict of interests.

Source: Kong J et al. Ann Hematol. 2021 Jul 19. doi: 10.1007/s00277-021-04606-9.

Key clinical point: Natural killer (NK) cell subsets, particularly CD56bright NK cells, were associated with relapse outcomes after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP). Moreover, interferon-a therapy gradually increased levels of CD56bright NK cells.

Major finding: Among patients who did not receive interferon-a therapy, the nonrelapsed vs relapsed patients had a significantly higher proportion of CD3-CD56+ NK cells (P = .016), particularly CD3-CD56dimCD16+ NK cells (P = .017), at 1 month after TKI discontinuation. Patients who received interferon-a therapy showed an increase in CD56bright NK cells at 3- and 6- months post-therapy vs pre-therapy (P < .05).

Study details: Findings are from a retrospective analysis of 34 patients with CML-CP who discontinued TKI therapy after 3 or more years and at least 2 years of MR4.5. Twelve patients received interferon-a therapy post-TKI discontinuation.

Disclosures: This study was supported by the Capital Characteristic Clinic Project Foundation. The authors declared no conflict of interests.

Source: Kong J et al. Ann Hematol. 2021 Jul 19. doi: 10.1007/s00277-021-04606-9.

Key clinical point: Natural killer (NK) cell subsets, particularly CD56bright NK cells, were associated with relapse outcomes after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP). Moreover, interferon-a therapy gradually increased levels of CD56bright NK cells.

Major finding: Among patients who did not receive interferon-a therapy, the nonrelapsed vs relapsed patients had a significantly higher proportion of CD3-CD56+ NK cells (P = .016), particularly CD3-CD56dimCD16+ NK cells (P = .017), at 1 month after TKI discontinuation. Patients who received interferon-a therapy showed an increase in CD56bright NK cells at 3- and 6- months post-therapy vs pre-therapy (P < .05).

Study details: Findings are from a retrospective analysis of 34 patients with CML-CP who discontinued TKI therapy after 3 or more years and at least 2 years of MR4.5. Twelve patients received interferon-a therapy post-TKI discontinuation.

Disclosures: This study was supported by the Capital Characteristic Clinic Project Foundation. The authors declared no conflict of interests.

Source: Kong J et al. Ann Hematol. 2021 Jul 19. doi: 10.1007/s00277-021-04606-9.

Key clinical point: Among patients with advanced phase chronic myeloid leukemia (CML), long-term survival after hematopoietic stem cell transplantation (HSCT) was influenced by donor age, CD34⁺ cell dose in the graft, and blast crisis (BC) at HSCT.

Major finding: At 15 years, overall survival (OS) and progression-free survival were 34% (95% confidence interval [CI], 22%-46%) and 26% (95% CI, 16%-36%), respectively. Donor age above 36 years (hazard ratio [HR], 1.74; P = .02), BC at HSCT (HR, 1.85; P = .01), and lower CD34⁺ cell dose in the graft (HR using continuous variables, 1.12; HR using categorical variables, 2.14; both P < .01) were associated with inferior OS.

Study details: Findings are from a retrospective analysis of 147 patients with advanced CML (BC, n=37; accelerated phase, n=40; second or higher chronic phase, n=70) who underwent HSCT between 1990 and 2018.

Disclosures: Open Access funding was enabled and organized by Projekt DEAL. The authors declared no conflict of interests.

Source: Niederwieser C et al. Bone Marrow Transplant. 2021 Jul 30. doi: 10.1038/s41409-021-01410-x.

Key clinical point: Among patients with advanced phase chronic myeloid leukemia (CML), long-term survival after hematopoietic stem cell transplantation (HSCT) was influenced by donor age, CD34⁺ cell dose in the graft, and blast crisis (BC) at HSCT.

Major finding: At 15 years, overall survival (OS) and progression-free survival were 34% (95% confidence interval [CI], 22%-46%) and 26% (95% CI, 16%-36%), respectively. Donor age above 36 years (hazard ratio [HR], 1.74; P = .02), BC at HSCT (HR, 1.85; P = .01), and lower CD34⁺ cell dose in the graft (HR using continuous variables, 1.12; HR using categorical variables, 2.14; both P < .01) were associated with inferior OS.

Study details: Findings are from a retrospective analysis of 147 patients with advanced CML (BC, n=37; accelerated phase, n=40; second or higher chronic phase, n=70) who underwent HSCT between 1990 and 2018.

Disclosures: Open Access funding was enabled and organized by Projekt DEAL. The authors declared no conflict of interests.

Source: Niederwieser C et al. Bone Marrow Transplant. 2021 Jul 30. doi: 10.1038/s41409-021-01410-x.

Key clinical point: Among patients with advanced phase chronic myeloid leukemia (CML), long-term survival after hematopoietic stem cell transplantation (HSCT) was influenced by donor age, CD34⁺ cell dose in the graft, and blast crisis (BC) at HSCT.

Major finding: At 15 years, overall survival (OS) and progression-free survival were 34% (95% confidence interval [CI], 22%-46%) and 26% (95% CI, 16%-36%), respectively. Donor age above 36 years (hazard ratio [HR], 1.74; P = .02), BC at HSCT (HR, 1.85; P = .01), and lower CD34⁺ cell dose in the graft (HR using continuous variables, 1.12; HR using categorical variables, 2.14; both P < .01) were associated with inferior OS.

Study details: Findings are from a retrospective analysis of 147 patients with advanced CML (BC, n=37; accelerated phase, n=40; second or higher chronic phase, n=70) who underwent HSCT between 1990 and 2018.

Disclosures: Open Access funding was enabled and organized by Projekt DEAL. The authors declared no conflict of interests.

Source: Niederwieser C et al. Bone Marrow Transplant. 2021 Jul 30. doi: 10.1038/s41409-021-01410-x.

Key clinical point: Thyroid abnormalities were more frequently observed in patients with chronic-phase chronic myeloid leukemia (CML-CP) on second-generation tyrosine kinase inhibitor (TKI) therapy vs imatinib and were associated with better treatment response.

Major finding: Hashimoto’s thyroiditis (HT; 30.4%) was more prevalent with nilotinib or dasatinib vs imatinib treatment (43.75% vs 18.9%; P = .03). The incidence of deep molecular response (DMR) was higher (73.1% vs 26.9%) and that of major molecular response (MMR) was lower (11.6% vs 88.4%) in patients with vs without thyroid alterations (P = .0001). HT was more prevalent in patients with DMR vs MMR (69.2% vs 7%; P = .0001).

Study details: Findings are from an analysis of 69 adult patients with Philadelphia chromosome-positive CML-CP treated with imatinib (n=37), nilotinib (n=21), or dasatinib (n=11) as first- or second-line therapy.

Disclosures: No funding was received for this study. Open access funding was provided by Universita degli Studi di Cagliari. The authors declared no conflict of interests.

Source: Rodia R et al. J Endocrinol Invest. 2021 Jul 20. doi: 10.1007/s40618-021-01613-5.

Key clinical point: Thyroid abnormalities were more frequently observed in patients with chronic-phase chronic myeloid leukemia (CML-CP) on second-generation tyrosine kinase inhibitor (TKI) therapy vs imatinib and were associated with better treatment response.

Major finding: Hashimoto’s thyroiditis (HT; 30.4%) was more prevalent with nilotinib or dasatinib vs imatinib treatment (43.75% vs 18.9%; P = .03). The incidence of deep molecular response (DMR) was higher (73.1% vs 26.9%) and that of major molecular response (MMR) was lower (11.6% vs 88.4%) in patients with vs without thyroid alterations (P = .0001). HT was more prevalent in patients with DMR vs MMR (69.2% vs 7%; P = .0001).

Study details: Findings are from an analysis of 69 adult patients with Philadelphia chromosome-positive CML-CP treated with imatinib (n=37), nilotinib (n=21), or dasatinib (n=11) as first- or second-line therapy.

Disclosures: No funding was received for this study. Open access funding was provided by Universita degli Studi di Cagliari. The authors declared no conflict of interests.

Source: Rodia R et al. J Endocrinol Invest. 2021 Jul 20. doi: 10.1007/s40618-021-01613-5.

Key clinical point: Thyroid abnormalities were more frequently observed in patients with chronic-phase chronic myeloid leukemia (CML-CP) on second-generation tyrosine kinase inhibitor (TKI) therapy vs imatinib and were associated with better treatment response.

Major finding: Hashimoto’s thyroiditis (HT; 30.4%) was more prevalent with nilotinib or dasatinib vs imatinib treatment (43.75% vs 18.9%; P = .03). The incidence of deep molecular response (DMR) was higher (73.1% vs 26.9%) and that of major molecular response (MMR) was lower (11.6% vs 88.4%) in patients with vs without thyroid alterations (P = .0001). HT was more prevalent in patients with DMR vs MMR (69.2% vs 7%; P = .0001).

Study details: Findings are from an analysis of 69 adult patients with Philadelphia chromosome-positive CML-CP treated with imatinib (n=37), nilotinib (n=21), or dasatinib (n=11) as first- or second-line therapy.

Disclosures: No funding was received for this study. Open access funding was provided by Universita degli Studi di Cagliari. The authors declared no conflict of interests.

Source: Rodia R et al. J Endocrinol Invest. 2021 Jul 20. doi: 10.1007/s40618-021-01613-5.