CML

Key clinical point: Among patients with myeloid blast phase chronic myeloid leukemia (CML-MBP), combination therapy of tyrosine kinase inhibitor (TKI) with intensive chemotherapy (IC) or hypomethylating agent (HMA) resulted in better clinical outcomes vs TKI alone.

Major finding: IC/HMA+TKI vs TKI alone resulted in higher rates of complete remission (CR) or CR with incomplete count recovery (57.5% vs 33.9%), complete cytogenic response (45.0% vs 10.7%), major/deep molecular response (24.2% vs 4.3%;), and more patients proceeding to allogeneic stem cell transplant (32.5% vs 10.7%). In patients receiving the second/third generation TKIs, IC/HMA+TKI led to superior 5-year event-free survival (28% vs 0%) and reduced relapse (44% vs 86%) vs TKI alone (all P less than .05).

Study details: Findings are from a retrospective analysis of 104 patients with CML-MBP receiving frontline treatment based on 4 different approaches, i.e., IC+TKI (n=20), HMA+TKI (n=20), TKI alone (n=56), or IC alone (n=8), between 2000 and 2019.

Disclosures: This study was supported by MD Anderson Cancer Center Support Grant and SPORE. NJ Short reported ties with various pharmaceutical companies. Other authors declared no competing interests.

Source: Saxena K et al. J Hematol Oncol. 2021 Jun 15. doi: 10.1186/s13045-021-01106-1.

Key clinical point: Among patients with myeloid blast phase chronic myeloid leukemia (CML-MBP), combination therapy of tyrosine kinase inhibitor (TKI) with intensive chemotherapy (IC) or hypomethylating agent (HMA) resulted in better clinical outcomes vs TKI alone.

Major finding: IC/HMA+TKI vs TKI alone resulted in higher rates of complete remission (CR) or CR with incomplete count recovery (57.5% vs 33.9%), complete cytogenic response (45.0% vs 10.7%), major/deep molecular response (24.2% vs 4.3%;), and more patients proceeding to allogeneic stem cell transplant (32.5% vs 10.7%). In patients receiving the second/third generation TKIs, IC/HMA+TKI led to superior 5-year event-free survival (28% vs 0%) and reduced relapse (44% vs 86%) vs TKI alone (all P less than .05).

Study details: Findings are from a retrospective analysis of 104 patients with CML-MBP receiving frontline treatment based on 4 different approaches, i.e., IC+TKI (n=20), HMA+TKI (n=20), TKI alone (n=56), or IC alone (n=8), between 2000 and 2019.

Disclosures: This study was supported by MD Anderson Cancer Center Support Grant and SPORE. NJ Short reported ties with various pharmaceutical companies. Other authors declared no competing interests.

Source: Saxena K et al. J Hematol Oncol. 2021 Jun 15. doi: 10.1186/s13045-021-01106-1.

Key clinical point: Among patients with myeloid blast phase chronic myeloid leukemia (CML-MBP), combination therapy of tyrosine kinase inhibitor (TKI) with intensive chemotherapy (IC) or hypomethylating agent (HMA) resulted in better clinical outcomes vs TKI alone.

Major finding: IC/HMA+TKI vs TKI alone resulted in higher rates of complete remission (CR) or CR with incomplete count recovery (57.5% vs 33.9%), complete cytogenic response (45.0% vs 10.7%), major/deep molecular response (24.2% vs 4.3%;), and more patients proceeding to allogeneic stem cell transplant (32.5% vs 10.7%). In patients receiving the second/third generation TKIs, IC/HMA+TKI led to superior 5-year event-free survival (28% vs 0%) and reduced relapse (44% vs 86%) vs TKI alone (all P less than .05).

Study details: Findings are from a retrospective analysis of 104 patients with CML-MBP receiving frontline treatment based on 4 different approaches, i.e., IC+TKI (n=20), HMA+TKI (n=20), TKI alone (n=56), or IC alone (n=8), between 2000 and 2019.

Disclosures: This study was supported by MD Anderson Cancer Center Support Grant and SPORE. NJ Short reported ties with various pharmaceutical companies. Other authors declared no competing interests.

Source: Saxena K et al. J Hematol Oncol. 2021 Jun 15. doi: 10.1186/s13045-021-01106-1.

Key clinical point: Presence of non-breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) mutations in patients with chronic myeloid leukemia (CML) was not associated with clinical outcomes.

Major finding: Non-BCR-ABL1 mutations were observed in 18% of patients with CML at diagnosis and were mostly cleared with TKI therapy, indicating an origin in the Philadelphia chromosome-positive clone. However, no difference was observed in overall survival, progression-free survival, failure-free survival, and adverse events between patients with vs without non-BCR-ABL1 mutations.

Study details: Findings are from next-generation sequencing analysis of BCR-ABL1 kinase domain and 18 myeloid neoplasm-associated genes in 49 patients with de novo chronic phase-CML and 6 healthy controls.

Disclosures: This study was supported by grants from the Ministry of Health of the Czech Republic, the Ministry of Education, and Bristol-Myers Squibb. D Zackova and J Mayer reported ties with various pharmaceutical companies including Bristol-Myers Squibb. Other authors declared no competing interests.

Source: Romzova M et al. Br J Haematol. 2021 Jul 1. doi: 10.1111/bjh.17659.

Key clinical point: Presence of non-breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) mutations in patients with chronic myeloid leukemia (CML) was not associated with clinical outcomes.

Major finding: Non-BCR-ABL1 mutations were observed in 18% of patients with CML at diagnosis and were mostly cleared with TKI therapy, indicating an origin in the Philadelphia chromosome-positive clone. However, no difference was observed in overall survival, progression-free survival, failure-free survival, and adverse events between patients with vs without non-BCR-ABL1 mutations.

Study details: Findings are from next-generation sequencing analysis of BCR-ABL1 kinase domain and 18 myeloid neoplasm-associated genes in 49 patients with de novo chronic phase-CML and 6 healthy controls.

Disclosures: This study was supported by grants from the Ministry of Health of the Czech Republic, the Ministry of Education, and Bristol-Myers Squibb. D Zackova and J Mayer reported ties with various pharmaceutical companies including Bristol-Myers Squibb. Other authors declared no competing interests.

Source: Romzova M et al. Br J Haematol. 2021 Jul 1. doi: 10.1111/bjh.17659.

Key clinical point: Presence of non-breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) mutations in patients with chronic myeloid leukemia (CML) was not associated with clinical outcomes.

Major finding: Non-BCR-ABL1 mutations were observed in 18% of patients with CML at diagnosis and were mostly cleared with TKI therapy, indicating an origin in the Philadelphia chromosome-positive clone. However, no difference was observed in overall survival, progression-free survival, failure-free survival, and adverse events between patients with vs without non-BCR-ABL1 mutations.

Study details: Findings are from next-generation sequencing analysis of BCR-ABL1 kinase domain and 18 myeloid neoplasm-associated genes in 49 patients with de novo chronic phase-CML and 6 healthy controls.

Disclosures: This study was supported by grants from the Ministry of Health of the Czech Republic, the Ministry of Education, and Bristol-Myers Squibb. D Zackova and J Mayer reported ties with various pharmaceutical companies including Bristol-Myers Squibb. Other authors declared no competing interests.

Source: Romzova M et al. Br J Haematol. 2021 Jul 1. doi: 10.1111/bjh.17659.

Key clinical point: Nilotinib treatment resulted in an early and stable clearance of CD34+/lin-Ph+ cells from the bone marrow of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 3, 6, and 12 months, only 12.3% (95% confidence interval [CI], 5.5%-22.8%), 7% (95% CI, 2.3%-15.7%), and 0% (95% CI, 0.0%-5.0%) samples, respectively, showed residual CD34+/lin-Ph+ cells, indicating rapid and sustained clearance of these cells from the bone marrow of treated patients.

Study details: Findings are from a prospective, single-arm, PhilosoPhi34 study including 87 adult patients with newly diagnosed Philadelphia chromosome-positive CML-CP treated with nilotinib 300 mg twice daily.

Disclosures: This study was partly supported by Novartis. The authors declared no conflicts of interest.

Source: Pungolino E et al. Eur J Haematol. 2021 Jun 17. doi: 10.1111/ejh.13680.

Key clinical point: Nilotinib treatment resulted in an early and stable clearance of CD34+/lin-Ph+ cells from the bone marrow of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 3, 6, and 12 months, only 12.3% (95% confidence interval [CI], 5.5%-22.8%), 7% (95% CI, 2.3%-15.7%), and 0% (95% CI, 0.0%-5.0%) samples, respectively, showed residual CD34+/lin-Ph+ cells, indicating rapid and sustained clearance of these cells from the bone marrow of treated patients.

Study details: Findings are from a prospective, single-arm, PhilosoPhi34 study including 87 adult patients with newly diagnosed Philadelphia chromosome-positive CML-CP treated with nilotinib 300 mg twice daily.

Disclosures: This study was partly supported by Novartis. The authors declared no conflicts of interest.

Source: Pungolino E et al. Eur J Haematol. 2021 Jun 17. doi: 10.1111/ejh.13680.

Key clinical point: Nilotinib treatment resulted in an early and stable clearance of CD34+/lin-Ph+ cells from the bone marrow of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 3, 6, and 12 months, only 12.3% (95% confidence interval [CI], 5.5%-22.8%), 7% (95% CI, 2.3%-15.7%), and 0% (95% CI, 0.0%-5.0%) samples, respectively, showed residual CD34+/lin-Ph+ cells, indicating rapid and sustained clearance of these cells from the bone marrow of treated patients.

Study details: Findings are from a prospective, single-arm, PhilosoPhi34 study including 87 adult patients with newly diagnosed Philadelphia chromosome-positive CML-CP treated with nilotinib 300 mg twice daily.

Disclosures: This study was partly supported by Novartis. The authors declared no conflicts of interest.

Source: Pungolino E et al. Eur J Haematol. 2021 Jun 17. doi: 10.1111/ejh.13680.

Key clinical point: Dasatinib dose optimization by therapeutic drug monitoring (TDM) during treatment initiation in patients with newly diagnosed chronic myeloid leukemia (CML) was feasible and led to a significant reduction in pleural effusion (PIEff) without affecting molecular responses.

Major finding: Reduced incidence of all-grade PlEff was observed in patients with high trough concentration [(C)min] who underwent dasatinib dose optimization by TDM (TDM arm; 13.2%) vs those who continued with standard dose (control arm; 42.8%) and those with low (C)min assigned to observation (observation arm; 17.4%; P = .006), with no major effect on major molecular response (P = .978) across the 3 arms.

Study details: Findings are from the phase 2 OPTIM-dasatinib study including 287 patients with newly diagnosed, previously untreated (except with hydroxycarbamide) CML. Patients were initially started on dasatinib 100 mg/day. After 7-10 days, patients with low (C)min were assigned to the observation arm (n=207) and those with high (C)min (3 nmol/L or higher) were randomly assigned to either TDM (n=38) or control (n=42) arms.

Disclosures: This study was funded by Bristol-Myers Squibb. The lead author reported research funding from Bristol-Myers Squibb, Pfizer, and Incyte.

Source: Rousselot P et al. Br J Haematol. 2021 Jun 30. doi: 10.1111/bjh.17654.

Key clinical point: Dasatinib dose optimization by therapeutic drug monitoring (TDM) during treatment initiation in patients with newly diagnosed chronic myeloid leukemia (CML) was feasible and led to a significant reduction in pleural effusion (PIEff) without affecting molecular responses.

Major finding: Reduced incidence of all-grade PlEff was observed in patients with high trough concentration [(C)min] who underwent dasatinib dose optimization by TDM (TDM arm; 13.2%) vs those who continued with standard dose (control arm; 42.8%) and those with low (C)min assigned to observation (observation arm; 17.4%; P = .006), with no major effect on major molecular response (P = .978) across the 3 arms.

Study details: Findings are from the phase 2 OPTIM-dasatinib study including 287 patients with newly diagnosed, previously untreated (except with hydroxycarbamide) CML. Patients were initially started on dasatinib 100 mg/day. After 7-10 days, patients with low (C)min were assigned to the observation arm (n=207) and those with high (C)min (3 nmol/L or higher) were randomly assigned to either TDM (n=38) or control (n=42) arms.

Disclosures: This study was funded by Bristol-Myers Squibb. The lead author reported research funding from Bristol-Myers Squibb, Pfizer, and Incyte.

Source: Rousselot P et al. Br J Haematol. 2021 Jun 30. doi: 10.1111/bjh.17654.

Key clinical point: Dasatinib dose optimization by therapeutic drug monitoring (TDM) during treatment initiation in patients with newly diagnosed chronic myeloid leukemia (CML) was feasible and led to a significant reduction in pleural effusion (PIEff) without affecting molecular responses.

Major finding: Reduced incidence of all-grade PlEff was observed in patients with high trough concentration [(C)min] who underwent dasatinib dose optimization by TDM (TDM arm; 13.2%) vs those who continued with standard dose (control arm; 42.8%) and those with low (C)min assigned to observation (observation arm; 17.4%; P = .006), with no major effect on major molecular response (P = .978) across the 3 arms.

Study details: Findings are from the phase 2 OPTIM-dasatinib study including 287 patients with newly diagnosed, previously untreated (except with hydroxycarbamide) CML. Patients were initially started on dasatinib 100 mg/day. After 7-10 days, patients with low (C)min were assigned to the observation arm (n=207) and those with high (C)min (3 nmol/L or higher) were randomly assigned to either TDM (n=38) or control (n=42) arms.

Disclosures: This study was funded by Bristol-Myers Squibb. The lead author reported research funding from Bristol-Myers Squibb, Pfizer, and Incyte.

Source: Rousselot P et al. Br J Haematol. 2021 Jun 30. doi: 10.1111/bjh.17654.

Key clinical point: Suboptimal responses to a single dose of Pfizer-BioNTech BNT162b2 or AstraZeneca ChAdOx1 nCoV-19 vaccines in patients with chronic myeloid neoplasms including chronic myeloid leukemia (CML) highlight a potentially important immunocompromise in this patient population.

Major finding: At 14 days after single vaccination dose, patients with chronic myeloid blood cancers vs health care workers above 60 years of age had significantly lower seroconversion (58% vs 97%) and median anti-S antibody titer (75 vs 630; both P less than .0001). Among disease subgroups, seroconversion was highest in patients with CML (75%) and observed in 83% of patients with CML receiving imatinib.

Study details: Findings are from a real-world analysis of 60 patients with myeloid cancers, including 12 patients with CML and no evidence of prior COVID-19 infection, who received a single dose of either BNT162b2 or ChAdOx1 nCoV-19 vaccines.

Disclosures: This study was funded by the National Institute of Health Research Oxford Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Chowdhury O et al. Br J Haematol. 2021 Jun 16. doi: 10.1111/bjh.17644.

Key clinical point: Suboptimal responses to a single dose of Pfizer-BioNTech BNT162b2 or AstraZeneca ChAdOx1 nCoV-19 vaccines in patients with chronic myeloid neoplasms including chronic myeloid leukemia (CML) highlight a potentially important immunocompromise in this patient population.

Major finding: At 14 days after single vaccination dose, patients with chronic myeloid blood cancers vs health care workers above 60 years of age had significantly lower seroconversion (58% vs 97%) and median anti-S antibody titer (75 vs 630; both P less than .0001). Among disease subgroups, seroconversion was highest in patients with CML (75%) and observed in 83% of patients with CML receiving imatinib.

Study details: Findings are from a real-world analysis of 60 patients with myeloid cancers, including 12 patients with CML and no evidence of prior COVID-19 infection, who received a single dose of either BNT162b2 or ChAdOx1 nCoV-19 vaccines.

Disclosures: This study was funded by the National Institute of Health Research Oxford Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Chowdhury O et al. Br J Haematol. 2021 Jun 16. doi: 10.1111/bjh.17644.

Key clinical point: Suboptimal responses to a single dose of Pfizer-BioNTech BNT162b2 or AstraZeneca ChAdOx1 nCoV-19 vaccines in patients with chronic myeloid neoplasms including chronic myeloid leukemia (CML) highlight a potentially important immunocompromise in this patient population.

Major finding: At 14 days after single vaccination dose, patients with chronic myeloid blood cancers vs health care workers above 60 years of age had significantly lower seroconversion (58% vs 97%) and median anti-S antibody titer (75 vs 630; both P less than .0001). Among disease subgroups, seroconversion was highest in patients with CML (75%) and observed in 83% of patients with CML receiving imatinib.

Study details: Findings are from a real-world analysis of 60 patients with myeloid cancers, including 12 patients with CML and no evidence of prior COVID-19 infection, who received a single dose of either BNT162b2 or ChAdOx1 nCoV-19 vaccines.

Disclosures: This study was funded by the National Institute of Health Research Oxford Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Chowdhury O et al. Br J Haematol. 2021 Jun 16. doi: 10.1111/bjh.17644.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation was feasible and safe not only at the first but also at the second attempt in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At the first attempt of TKI discontinuation, 28 patients achieved sustained treatment-free remission (TFR, 53.4%; 95% confidence interval [CI], 39.0%-65.9%) at 1 year. Among the 10 patients who attempted the second TKI discontinuation, 4 achieved the second TFR at 1 year (TFR, 37.5%; 95% CI, 9.9%-65.9%). Other 6 patients with the second relapse achieved at least a major molecular response within 6 months after resuming TKI treatment.

Study details: Findings are from a retrospective analysis of 53 patients with Philadelphia chromosome-positive CML-CP who attempted TKI discontinuation following a durable deep molecular response on TKI therapy.

Disclosures: This work was supported by the Shinnihon Foundation of Advanced Medical Treatment Research, Okinaka Memorial Institute for Medical Research, and the Japan Society for the Promotion of Science. S Kimura reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ureshino H et al. Hematol Oncol. 2021 Jun 11. doi: 10.1002/hon.2896.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation was feasible and safe not only at the first but also at the second attempt in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At the first attempt of TKI discontinuation, 28 patients achieved sustained treatment-free remission (TFR, 53.4%; 95% confidence interval [CI], 39.0%-65.9%) at 1 year. Among the 10 patients who attempted the second TKI discontinuation, 4 achieved the second TFR at 1 year (TFR, 37.5%; 95% CI, 9.9%-65.9%). Other 6 patients with the second relapse achieved at least a major molecular response within 6 months after resuming TKI treatment.

Study details: Findings are from a retrospective analysis of 53 patients with Philadelphia chromosome-positive CML-CP who attempted TKI discontinuation following a durable deep molecular response on TKI therapy.

Disclosures: This work was supported by the Shinnihon Foundation of Advanced Medical Treatment Research, Okinaka Memorial Institute for Medical Research, and the Japan Society for the Promotion of Science. S Kimura reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ureshino H et al. Hematol Oncol. 2021 Jun 11. doi: 10.1002/hon.2896.

Key clinical point: Tyrosine kinase inhibitor (TKI) discontinuation was feasible and safe not only at the first but also at the second attempt in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At the first attempt of TKI discontinuation, 28 patients achieved sustained treatment-free remission (TFR, 53.4%; 95% confidence interval [CI], 39.0%-65.9%) at 1 year. Among the 10 patients who attempted the second TKI discontinuation, 4 achieved the second TFR at 1 year (TFR, 37.5%; 95% CI, 9.9%-65.9%). Other 6 patients with the second relapse achieved at least a major molecular response within 6 months after resuming TKI treatment.

Study details: Findings are from a retrospective analysis of 53 patients with Philadelphia chromosome-positive CML-CP who attempted TKI discontinuation following a durable deep molecular response on TKI therapy.

Disclosures: This work was supported by the Shinnihon Foundation of Advanced Medical Treatment Research, Okinaka Memorial Institute for Medical Research, and the Japan Society for the Promotion of Science. S Kimura reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ureshino H et al. Hematol Oncol. 2021 Jun 11. doi: 10.1002/hon.2896.

Key clinical point: Among patients with chronic myeloid leukemia (CML), the mean daily dose of nilotinib, either as the first- or second-line treatment prescribed in Italian clinical practice settings, was lower than the approved dose reported in the summary of product characteristics as the first- (600 mg daily) and second-line (800 mg daily) treatment.

Major finding: Based on the last determination of the BCR/ABL test, the mean daily nilotinib dose was 498.54 mg (mean treatment duration, 811 days) and 565.2 mg (mean treatment duration, 323.1 days) for patients treated with first- and second-line nilotinib, respectively.

Study details: Findings are from a retrospective analysis of adult patients with CML receiving either first-line nilotinib between January 2013 and December 2016 (n=87) or second-line nilotinib between January 2015 and December 2018 (n=103).

Disclosures: This publication was funded by Novartis Farma S.p.A. The authors declared no conflicts of interest.

Source: Perrone V et al. Ther Clin Risk Manag. 2021 Jun 8. doi: 10.2147/TCRM.S309342.

Key clinical point: Among patients with chronic myeloid leukemia (CML), the mean daily dose of nilotinib, either as the first- or second-line treatment prescribed in Italian clinical practice settings, was lower than the approved dose reported in the summary of product characteristics as the first- (600 mg daily) and second-line (800 mg daily) treatment.

Major finding: Based on the last determination of the BCR/ABL test, the mean daily nilotinib dose was 498.54 mg (mean treatment duration, 811 days) and 565.2 mg (mean treatment duration, 323.1 days) for patients treated with first- and second-line nilotinib, respectively.

Study details: Findings are from a retrospective analysis of adult patients with CML receiving either first-line nilotinib between January 2013 and December 2016 (n=87) or second-line nilotinib between January 2015 and December 2018 (n=103).

Disclosures: This publication was funded by Novartis Farma S.p.A. The authors declared no conflicts of interest.

Source: Perrone V et al. Ther Clin Risk Manag. 2021 Jun 8. doi: 10.2147/TCRM.S309342.

Key clinical point: Among patients with chronic myeloid leukemia (CML), the mean daily dose of nilotinib, either as the first- or second-line treatment prescribed in Italian clinical practice settings, was lower than the approved dose reported in the summary of product characteristics as the first- (600 mg daily) and second-line (800 mg daily) treatment.

Major finding: Based on the last determination of the BCR/ABL test, the mean daily nilotinib dose was 498.54 mg (mean treatment duration, 811 days) and 565.2 mg (mean treatment duration, 323.1 days) for patients treated with first- and second-line nilotinib, respectively.

Study details: Findings are from a retrospective analysis of adult patients with CML receiving either first-line nilotinib between January 2013 and December 2016 (n=87) or second-line nilotinib between January 2015 and December 2018 (n=103).

Disclosures: This publication was funded by Novartis Farma S.p.A. The authors declared no conflicts of interest.

Source: Perrone V et al. Ther Clin Risk Manag. 2021 Jun 8. doi: 10.2147/TCRM.S309342.

Key clinical point: Inotuzumab ozogamicin with bosutinib was well tolerated in patients with relapsed/refractory (R/R) lymphoid blast phase of chronic myeloid leukemia (CML-LBP) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

Major finding: Rates of complete response (CR)/CR with incomplete count recovery, complete cytogenic response, measurable residual disease negativity, and complete molecular response were 83%, 81%, 61%, and 56%, respectively. The 30-day mortality was 0%. During the median follow-up of 44 months, median event-free survival and overall survival were 7.7 and 13.5 months, respectively. No patients discontinued treatment because of toxicity, and no veno-occlusive disease was reported.

Study details: This was a phase 1/2 trial including 18 patients with R/R Ph+ALL (n=16) or CML-LBP (n=2). The maximum tolerated dose of bosutinib was 400 mg daily.

Disclosures: This study was funded by Pfizer, MD Anderson Cancer Center Support Grant, and the National Cancer Institute. Some investigators including the lead author reported ties with various pharmaceutical companies, including Pfizer.

Source: Jain N et al. Am J Hematol. 2021 May 15. doi: 10.1002/ajh.26238.

Key clinical point: Inotuzumab ozogamicin with bosutinib was well tolerated in patients with relapsed/refractory (R/R) lymphoid blast phase of chronic myeloid leukemia (CML-LBP) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

Major finding: Rates of complete response (CR)/CR with incomplete count recovery, complete cytogenic response, measurable residual disease negativity, and complete molecular response were 83%, 81%, 61%, and 56%, respectively. The 30-day mortality was 0%. During the median follow-up of 44 months, median event-free survival and overall survival were 7.7 and 13.5 months, respectively. No patients discontinued treatment because of toxicity, and no veno-occlusive disease was reported.

Study details: This was a phase 1/2 trial including 18 patients with R/R Ph+ALL (n=16) or CML-LBP (n=2). The maximum tolerated dose of bosutinib was 400 mg daily.

Disclosures: This study was funded by Pfizer, MD Anderson Cancer Center Support Grant, and the National Cancer Institute. Some investigators including the lead author reported ties with various pharmaceutical companies, including Pfizer.

Source: Jain N et al. Am J Hematol. 2021 May 15. doi: 10.1002/ajh.26238.

Key clinical point: Inotuzumab ozogamicin with bosutinib was well tolerated in patients with relapsed/refractory (R/R) lymphoid blast phase of chronic myeloid leukemia (CML-LBP) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

Major finding: Rates of complete response (CR)/CR with incomplete count recovery, complete cytogenic response, measurable residual disease negativity, and complete molecular response were 83%, 81%, 61%, and 56%, respectively. The 30-day mortality was 0%. During the median follow-up of 44 months, median event-free survival and overall survival were 7.7 and 13.5 months, respectively. No patients discontinued treatment because of toxicity, and no veno-occlusive disease was reported.

Study details: This was a phase 1/2 trial including 18 patients with R/R Ph+ALL (n=16) or CML-LBP (n=2). The maximum tolerated dose of bosutinib was 400 mg daily.

Disclosures: This study was funded by Pfizer, MD Anderson Cancer Center Support Grant, and the National Cancer Institute. Some investigators including the lead author reported ties with various pharmaceutical companies, including Pfizer.

Source: Jain N et al. Am J Hematol. 2021 May 15. doi: 10.1002/ajh.26238.

Key clinical point: Polymorphisms of CYP2A6 and ABCC4 genes were associated with a protective effect against the development of chronic myeloid leukemia (CML). These findings highlight the underlying genetic predisposition of individuals to develop CML.

Major finding: Individuals with the C allele of the rs28399433 polymorphism of CYP2A6 gene (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.78; P = .008) and the CC genotype of the rs3742106 polymorphism of ABCC4 gene (OR, 0.30; 95% CI, 0.10-0.88; P = .020) had a significantly reduced susceptibility to CML vs. other genotypes.

Study details: This retrospective study assessed an admixed population of 269 individuals including 143 patients with CML and 126 healthy controls from the Amazon region of Brazil.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Monte N et al. Mol Genet Genomic Med. 2021 May 29. doi: 10.1002/mgg3.1694.

Key clinical point: Polymorphisms of CYP2A6 and ABCC4 genes were associated with a protective effect against the development of chronic myeloid leukemia (CML). These findings highlight the underlying genetic predisposition of individuals to develop CML.

Major finding: Individuals with the C allele of the rs28399433 polymorphism of CYP2A6 gene (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.78; P = .008) and the CC genotype of the rs3742106 polymorphism of ABCC4 gene (OR, 0.30; 95% CI, 0.10-0.88; P = .020) had a significantly reduced susceptibility to CML vs. other genotypes.

Study details: This retrospective study assessed an admixed population of 269 individuals including 143 patients with CML and 126 healthy controls from the Amazon region of Brazil.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Monte N et al. Mol Genet Genomic Med. 2021 May 29. doi: 10.1002/mgg3.1694.

Key clinical point: Polymorphisms of CYP2A6 and ABCC4 genes were associated with a protective effect against the development of chronic myeloid leukemia (CML). These findings highlight the underlying genetic predisposition of individuals to develop CML.

Major finding: Individuals with the C allele of the rs28399433 polymorphism of CYP2A6 gene (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.78; P = .008) and the CC genotype of the rs3742106 polymorphism of ABCC4 gene (OR, 0.30; 95% CI, 0.10-0.88; P = .020) had a significantly reduced susceptibility to CML vs. other genotypes.

Study details: This retrospective study assessed an admixed population of 269 individuals including 143 patients with CML and 126 healthy controls from the Amazon region of Brazil.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Monte N et al. Mol Genet Genomic Med. 2021 May 29. doi: 10.1002/mgg3.1694.

Key clinical point: The Eutos long-term survival (ELTS) score appeared better at predicting overall survival (OS) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), redefining the risk stratification obtained with the Sokal score. Patients defined as high risk by ELTS showed poorer OS, thereby warranting treatment intensification and close monitoring.

Major finding: A prognostic refinement was observed from the Sokal to the ELTS score in high and intermediate Sokal risk patients. In the high-risk Sokal group, 3-year OS ranged from 94.8% to 82.4% for patients considered at ‘true’ high risk. In the intermediate Sokal risk group, 3-year OS of high-risk patients was only 70.7% vs. 95.4% for low-risk and 87.9% for ‘true’ intermediate-risk patients.

Study details: Findings are from the analysis of 1,206 patients with CML from the GIMEMA observational study. Patients were treated with either imatinib (n=608) or second-generation TKIs, dasatinib, or nilotinib (n=598).

Disclosures: No source of funding was identified. Some investigators including the lead author reported honoraria from various pharmaceutical companies.

Source: Breccia M et al. Leukemia. 2021 May 17. doi: 10.1038/s41375-021-01292-4.

Key clinical point: The Eutos long-term survival (ELTS) score appeared better at predicting overall survival (OS) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), redefining the risk stratification obtained with the Sokal score. Patients defined as high risk by ELTS showed poorer OS, thereby warranting treatment intensification and close monitoring.

Major finding: A prognostic refinement was observed from the Sokal to the ELTS score in high and intermediate Sokal risk patients. In the high-risk Sokal group, 3-year OS ranged from 94.8% to 82.4% for patients considered at ‘true’ high risk. In the intermediate Sokal risk group, 3-year OS of high-risk patients was only 70.7% vs. 95.4% for low-risk and 87.9% for ‘true’ intermediate-risk patients.

Study details: Findings are from the analysis of 1,206 patients with CML from the GIMEMA observational study. Patients were treated with either imatinib (n=608) or second-generation TKIs, dasatinib, or nilotinib (n=598).

Disclosures: No source of funding was identified. Some investigators including the lead author reported honoraria from various pharmaceutical companies.

Source: Breccia M et al. Leukemia. 2021 May 17. doi: 10.1038/s41375-021-01292-4.

Key clinical point: The Eutos long-term survival (ELTS) score appeared better at predicting overall survival (OS) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), redefining the risk stratification obtained with the Sokal score. Patients defined as high risk by ELTS showed poorer OS, thereby warranting treatment intensification and close monitoring.

Major finding: A prognostic refinement was observed from the Sokal to the ELTS score in high and intermediate Sokal risk patients. In the high-risk Sokal group, 3-year OS ranged from 94.8% to 82.4% for patients considered at ‘true’ high risk. In the intermediate Sokal risk group, 3-year OS of high-risk patients was only 70.7% vs. 95.4% for low-risk and 87.9% for ‘true’ intermediate-risk patients.

Study details: Findings are from the analysis of 1,206 patients with CML from the GIMEMA observational study. Patients were treated with either imatinib (n=608) or second-generation TKIs, dasatinib, or nilotinib (n=598).

Disclosures: No source of funding was identified. Some investigators including the lead author reported honoraria from various pharmaceutical companies.

Source: Breccia M et al. Leukemia. 2021 May 17. doi: 10.1038/s41375-021-01292-4.