AML

This month, two studies reported on the addition of novel therapies to the backbone of low dose cytarabine. The first study, evaluated the role of adding quizartinib to low-dose cytarabine (LDAC) in older patients with acute myeloid leukemia (AML) not suitable for intensive chemotherapy. The addition of quizartinib to LDAC vs. LDAC alone improved survival and response in older patients with AML with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC). Among patients with FLT3-ITD mutation, LDAC+quizartinib improved response in 38% of patients vs. 0% of patients receiving LDAC alone (P = .02). The 2-year overall survival also improved significantly in patients receiving LDAC+quizartinib (hazard ratio [HR] 0.36; P = .024). The study included 202 older patients with AML (de novo AML 63%; secondary AML 25%; high-risk myelodysplastic syndrome 11%) unsuitable for IC with (n = 27) or without FLT3-ITD mutation randomly assigned to receive LDAC+quizartinib or LDAC alone.¹

The second study evaluated the combination of LDAC with venetoclax vs. placebo in treatment-naive patients with AML ineligible for IC. LDAC+venetoclax vs. LDAC+placebo improved median overall survival (HR 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002). This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).²This study was previously reported with a shorter follow up and ddi not demonstrate a survival difference for LDAC+venetoclax vs. LDAC alone. It is very reassuring to see these results with longer follow-up with an improvement of the median overall survival from 4.1 months with LDAC alone to 8.4 months with LDAC+venetoclax. In addition, responses were seen in patients who had prior hypomethylating agents. The CR, CR/CRi and CR/CR with partial hematologic recovery (CRh) rates were 7%, 29%, and 21% respectively.

Finally in a study by Roboz et al. patients who received oral azacytidine as maintenance had no worsening of fatigue or health-related quality of life. Maintenance therapy with oral azacitidine (oral-AZA) did not negatively affect fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC). Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo. Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC. One caveat is that the assessments were performed on Day 1 of each 28 day cycle, which may have allowed for the recovery from side effects of oral azacytidine.³

References

1. Dennis M et al. Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Adv. 2021 Oct 1.
2. Wei AH et al. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy. Blood Cancer J. 2021;11:163.
3. Roboz GJ et al. Oral azacitidine preserves favorable level of fatigue and health-related quality of life for patients with acute myeloid leukemia in remission: results from the phase 3, placebo-controlled QUAZAR AML-001 trial. Haematologica. 2021 Sep 23.

This month, two studies reported on the addition of novel therapies to the backbone of low dose cytarabine. The first study, evaluated the role of adding quizartinib to low-dose cytarabine (LDAC) in older patients with acute myeloid leukemia (AML) not suitable for intensive chemotherapy. The addition of quizartinib to LDAC vs. LDAC alone improved survival and response in older patients with AML with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC). Among patients with FLT3-ITD mutation, LDAC+quizartinib improved response in 38% of patients vs. 0% of patients receiving LDAC alone (P = .02). The 2-year overall survival also improved significantly in patients receiving LDAC+quizartinib (hazard ratio [HR] 0.36; P = .024). The study included 202 older patients with AML (de novo AML 63%; secondary AML 25%; high-risk myelodysplastic syndrome 11%) unsuitable for IC with (n = 27) or without FLT3-ITD mutation randomly assigned to receive LDAC+quizartinib or LDAC alone.¹

The second study evaluated the combination of LDAC with venetoclax vs. placebo in treatment-naive patients with AML ineligible for IC. LDAC+venetoclax vs. LDAC+placebo improved median overall survival (HR 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002). This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).²This study was previously reported with a shorter follow up and ddi not demonstrate a survival difference for LDAC+venetoclax vs. LDAC alone. It is very reassuring to see these results with longer follow-up with an improvement of the median overall survival from 4.1 months with LDAC alone to 8.4 months with LDAC+venetoclax. In addition, responses were seen in patients who had prior hypomethylating agents. The CR, CR/CRi and CR/CR with partial hematologic recovery (CRh) rates were 7%, 29%, and 21% respectively.

Finally in a study by Roboz et al. patients who received oral azacytidine as maintenance had no worsening of fatigue or health-related quality of life. Maintenance therapy with oral azacitidine (oral-AZA) did not negatively affect fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC). Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo. Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC. One caveat is that the assessments were performed on Day 1 of each 28 day cycle, which may have allowed for the recovery from side effects of oral azacytidine.³

References

1. Dennis M et al. Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Adv. 2021 Oct 1.
2. Wei AH et al. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy. Blood Cancer J. 2021;11:163.
3. Roboz GJ et al. Oral azacitidine preserves favorable level of fatigue and health-related quality of life for patients with acute myeloid leukemia in remission: results from the phase 3, placebo-controlled QUAZAR AML-001 trial. Haematologica. 2021 Sep 23.

This month, two studies reported on the addition of novel therapies to the backbone of low dose cytarabine. The first study, evaluated the role of adding quizartinib to low-dose cytarabine (LDAC) in older patients with acute myeloid leukemia (AML) not suitable for intensive chemotherapy. The addition of quizartinib to LDAC vs. LDAC alone improved survival and response in older patients with AML with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC). Among patients with FLT3-ITD mutation, LDAC+quizartinib improved response in 38% of patients vs. 0% of patients receiving LDAC alone (P = .02). The 2-year overall survival also improved significantly in patients receiving LDAC+quizartinib (hazard ratio [HR] 0.36; P = .024). The study included 202 older patients with AML (de novo AML 63%; secondary AML 25%; high-risk myelodysplastic syndrome 11%) unsuitable for IC with (n = 27) or without FLT3-ITD mutation randomly assigned to receive LDAC+quizartinib or LDAC alone.¹

The second study evaluated the combination of LDAC with venetoclax vs. placebo in treatment-naive patients with AML ineligible for IC. LDAC+venetoclax vs. LDAC+placebo improved median overall survival (HR 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (CRi) (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002). This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).²This study was previously reported with a shorter follow up and ddi not demonstrate a survival difference for LDAC+venetoclax vs. LDAC alone. It is very reassuring to see these results with longer follow-up with an improvement of the median overall survival from 4.1 months with LDAC alone to 8.4 months with LDAC+venetoclax. In addition, responses were seen in patients who had prior hypomethylating agents. The CR, CR/CRi and CR/CR with partial hematologic recovery (CRh) rates were 7%, 29%, and 21% respectively.

Finally in a study by Roboz et al. patients who received oral azacytidine as maintenance had no worsening of fatigue or health-related quality of life. Maintenance therapy with oral azacitidine (oral-AZA) did not negatively affect fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC). Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo. Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC. One caveat is that the assessments were performed on Day 1 of each 28 day cycle, which may have allowed for the recovery from side effects of oral azacytidine.³

References

1. Dennis M et al. Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Adv. 2021 Oct 1.
2. Wei AH et al. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy. Blood Cancer J. 2021;11:163.
3. Roboz GJ et al. Oral azacitidine preserves favorable level of fatigue and health-related quality of life for patients with acute myeloid leukemia in remission: results from the phase 3, placebo-controlled QUAZAR AML-001 trial. Haematologica. 2021 Sep 23.

Key clinical point: A dose of 300 mg secukinumab was more effective than 150 mg secukinumab, along with a similar safety profile in patients with psoriatic arthritis (PsA), particularly those who had an inadequate response to tumor necrosis factor inhibitors (anti-TNF-IR).

Major finding: At week 24, 20% or higher improvement in American College of Rheumatology (ACR20) response (odds ratio [OR] 1.41; P = .01) and resolution of dactylitis (OR 1.42; P = .02) was higher with 300 mg vs. 150 mg secukinumab. The proportion of ACR20 responders was higher with 300 mg vs. 150 mg secukinumab in anti-TNF-IR patients at weeks 24 (OR 1.75; P = .01) and 52 (OR 1.66; P = .01). The risk for adverse events was similar with both doses.

Study details: Findings are from a meta-analysis of 6 studies including 3 randomized controlled trials and 1,141 patients with PsA that compared 300 mg secukinumab (n = 461) vs. 150 mg secukinumab (n = 680).

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

Source: Zhang KL et al. Clinics (Sao Paulo). 2021 (Sep 20);76:e2820. doi: 10.6061/clinics/2021/e2820.

Key clinical point: A dose of 300 mg secukinumab was more effective than 150 mg secukinumab, along with a similar safety profile in patients with psoriatic arthritis (PsA), particularly those who had an inadequate response to tumor necrosis factor inhibitors (anti-TNF-IR).

Major finding: At week 24, 20% or higher improvement in American College of Rheumatology (ACR20) response (odds ratio [OR] 1.41; P = .01) and resolution of dactylitis (OR 1.42; P = .02) was higher with 300 mg vs. 150 mg secukinumab. The proportion of ACR20 responders was higher with 300 mg vs. 150 mg secukinumab in anti-TNF-IR patients at weeks 24 (OR 1.75; P = .01) and 52 (OR 1.66; P = .01). The risk for adverse events was similar with both doses.

Study details: Findings are from a meta-analysis of 6 studies including 3 randomized controlled trials and 1,141 patients with PsA that compared 300 mg secukinumab (n = 461) vs. 150 mg secukinumab (n = 680).

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

Source: Zhang KL et al. Clinics (Sao Paulo). 2021 (Sep 20);76:e2820. doi: 10.6061/clinics/2021/e2820.

Key clinical point: A dose of 300 mg secukinumab was more effective than 150 mg secukinumab, along with a similar safety profile in patients with psoriatic arthritis (PsA), particularly those who had an inadequate response to tumor necrosis factor inhibitors (anti-TNF-IR).

Major finding: At week 24, 20% or higher improvement in American College of Rheumatology (ACR20) response (odds ratio [OR] 1.41; P = .01) and resolution of dactylitis (OR 1.42; P = .02) was higher with 300 mg vs. 150 mg secukinumab. The proportion of ACR20 responders was higher with 300 mg vs. 150 mg secukinumab in anti-TNF-IR patients at weeks 24 (OR 1.75; P = .01) and 52 (OR 1.66; P = .01). The risk for adverse events was similar with both doses.

Study details: Findings are from a meta-analysis of 6 studies including 3 randomized controlled trials and 1,141 patients with PsA that compared 300 mg secukinumab (n = 461) vs. 150 mg secukinumab (n = 680).

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

Source: Zhang KL et al. Clinics (Sao Paulo). 2021 (Sep 20);76:e2820. doi: 10.6061/clinics/2021/e2820.

Key clinical point: Risk classification at acute myeloid leukemia (AML) diagnosis predicted clinical outcomes in patients with or without KMT2A-rearranged AML who underwent allogeneic hematopoietic cell transplant (HCT) in the first complete remission (CR1).

Major finding: Transplanted patients with KMT2A-rearranged and adverse-risk AML had worse overall survival (hazard ratio [HR] 1.32, and HR 1.45; both P < .001, respectively), leukemia-free survival (HR 1.26; P = .002, and HR 1.47; P < .001, respectively), and relapse (HR 1.27; P = .01, and HR 1.71; P < .001, respectively) vs. patients with intermediate-risk AML.

Study details: This retrospective registry-based study included 3,779 adult patients with KMT2A-rearranged (n = 426), non-KMT2A intermediate-risk (n = 2,384), or non-KMT2A adverse risk (n = 969) AML who underwent HCT in CR1.

Disclosures: This study was funded by Weinberg Family and Mortimer J. Lacher fellowships, American Society of Clinical Oncology Young Investigator Award, National Institutes of Health K12 Paul Calabresi Career Development Award for Clinical Oncology, and others. Some investigators reported receiving personal fees, grants, nonfinancial support, research collaboration, owning stocks, or other relations with various sources including pharmaceutical companies not connected with this study.

Source: Menghrajani K et al. Blood Adv. 2021 Sep 22. doi: 10.1182/bloodadvances.2021004881.

Key clinical point: Risk classification at acute myeloid leukemia (AML) diagnosis predicted clinical outcomes in patients with or without KMT2A-rearranged AML who underwent allogeneic hematopoietic cell transplant (HCT) in the first complete remission (CR1).

Major finding: Transplanted patients with KMT2A-rearranged and adverse-risk AML had worse overall survival (hazard ratio [HR] 1.32, and HR 1.45; both P < .001, respectively), leukemia-free survival (HR 1.26; P = .002, and HR 1.47; P < .001, respectively), and relapse (HR 1.27; P = .01, and HR 1.71; P < .001, respectively) vs. patients with intermediate-risk AML.

Study details: This retrospective registry-based study included 3,779 adult patients with KMT2A-rearranged (n = 426), non-KMT2A intermediate-risk (n = 2,384), or non-KMT2A adverse risk (n = 969) AML who underwent HCT in CR1.

Disclosures: This study was funded by Weinberg Family and Mortimer J. Lacher fellowships, American Society of Clinical Oncology Young Investigator Award, National Institutes of Health K12 Paul Calabresi Career Development Award for Clinical Oncology, and others. Some investigators reported receiving personal fees, grants, nonfinancial support, research collaboration, owning stocks, or other relations with various sources including pharmaceutical companies not connected with this study.

Source: Menghrajani K et al. Blood Adv. 2021 Sep 22. doi: 10.1182/bloodadvances.2021004881.

Key clinical point: Risk classification at acute myeloid leukemia (AML) diagnosis predicted clinical outcomes in patients with or without KMT2A-rearranged AML who underwent allogeneic hematopoietic cell transplant (HCT) in the first complete remission (CR1).

Major finding: Transplanted patients with KMT2A-rearranged and adverse-risk AML had worse overall survival (hazard ratio [HR] 1.32, and HR 1.45; both P < .001, respectively), leukemia-free survival (HR 1.26; P = .002, and HR 1.47; P < .001, respectively), and relapse (HR 1.27; P = .01, and HR 1.71; P < .001, respectively) vs. patients with intermediate-risk AML.

Study details: This retrospective registry-based study included 3,779 adult patients with KMT2A-rearranged (n = 426), non-KMT2A intermediate-risk (n = 2,384), or non-KMT2A adverse risk (n = 969) AML who underwent HCT in CR1.

Disclosures: This study was funded by Weinberg Family and Mortimer J. Lacher fellowships, American Society of Clinical Oncology Young Investigator Award, National Institutes of Health K12 Paul Calabresi Career Development Award for Clinical Oncology, and others. Some investigators reported receiving personal fees, grants, nonfinancial support, research collaboration, owning stocks, or other relations with various sources including pharmaceutical companies not connected with this study.

Source: Menghrajani K et al. Blood Adv. 2021 Sep 22. doi: 10.1182/bloodadvances.2021004881.

Key clinical point: Maintenance therapy with oral azacitidine (oral-AZA) did not compromise on fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC).

Major finding: Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo.

Study details: Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC.

Disclosures: This study was funded by Celgene, a Bristol Myers Squibb (BMS) Company. Some investigators, including the lead author, reported receiving research/personal support or consulting from, being an employee of, and owning equity in various sources, including Celgene and BMS.

Source: Roboz GJ et al. Haematologica. 2021 Sep 23. doi: 10.3324/haematol.2021.279174.

Key clinical point: Maintenance therapy with oral azacitidine (oral-AZA) did not compromise on fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC).

Major finding: Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo.

Study details: Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC.

Disclosures: This study was funded by Celgene, a Bristol Myers Squibb (BMS) Company. Some investigators, including the lead author, reported receiving research/personal support or consulting from, being an employee of, and owning equity in various sources, including Celgene and BMS.

Source: Roboz GJ et al. Haematologica. 2021 Sep 23. doi: 10.3324/haematol.2021.279174.

Key clinical point: Maintenance therapy with oral azacitidine (oral-AZA) did not compromise on fatigue and health-related quality of life (HrQoL) in patients with acute myeloid leukemia (AML) in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC).

Major finding: Effects of oral-AZA on fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue: difference in overall least square mean change [D] −0.89; 95% CI −2.37- 0.59) and HrQoL (EQ-5D-3L health utility index: D −0.01; 95% CI, −0.03-0.01; EQ-5D visual analog: D −0.95; 95% CI, −4.38-2.47) were comparable to placebo.

Study details: Findings are from the QUAZAR AML-001 trial, including 444 patients with AML with intermediate- or poor-risk cytogenetics at diagnosis and unsuitable for transplantation. The patients were randomly assigned to receive either oral-AZA (n = 225) or placebo (n = 219) in first CR/CRi after IC.

Disclosures: This study was funded by Celgene, a Bristol Myers Squibb (BMS) Company. Some investigators, including the lead author, reported receiving research/personal support or consulting from, being an employee of, and owning equity in various sources, including Celgene and BMS.

Source: Roboz GJ et al. Haematologica. 2021 Sep 23. doi: 10.3324/haematol.2021.279174.

Key clinical point: The source of COVID-19 in most patients with acute myeloid leukemia (AML) was presumed to be in-hospital transmission with mortality because COVID-19 was higher in patients with active disease than those in remission.

Major finding: The source of infection was in-hospital transmission in 63% of cases. The overall rate of mortality was 54.5%, with a higher incidence in patients with active AML vs. those in AML remission (83% vs. 17%; P = .0052).

Study details: This retrospective survey evaluated the response of 10 Brazilian hematologists representing 10 cancer centers, providing data on 33 adult patients with either active AML (n = 20) or in AML remission (n = 13) and a confirmed COVID-19 diagnosis. The patients were admitted to the hospital mainly through urgent or emergency care units.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Fagundes EM et al. Ann Hematol. 2021 Sep 17. doi:  10.1007/s00277-021-04659-w.

Key clinical point: The source of COVID-19 in most patients with acute myeloid leukemia (AML) was presumed to be in-hospital transmission with mortality because COVID-19 was higher in patients with active disease than those in remission.

Major finding: The source of infection was in-hospital transmission in 63% of cases. The overall rate of mortality was 54.5%, with a higher incidence in patients with active AML vs. those in AML remission (83% vs. 17%; P = .0052).

Study details: This retrospective survey evaluated the response of 10 Brazilian hematologists representing 10 cancer centers, providing data on 33 adult patients with either active AML (n = 20) or in AML remission (n = 13) and a confirmed COVID-19 diagnosis. The patients were admitted to the hospital mainly through urgent or emergency care units.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Fagundes EM et al. Ann Hematol. 2021 Sep 17. doi:  10.1007/s00277-021-04659-w.

Key clinical point: The source of COVID-19 in most patients with acute myeloid leukemia (AML) was presumed to be in-hospital transmission with mortality because COVID-19 was higher in patients with active disease than those in remission.

Major finding: The source of infection was in-hospital transmission in 63% of cases. The overall rate of mortality was 54.5%, with a higher incidence in patients with active AML vs. those in AML remission (83% vs. 17%; P = .0052).

Study details: This retrospective survey evaluated the response of 10 Brazilian hematologists representing 10 cancer centers, providing data on 33 adult patients with either active AML (n = 20) or in AML remission (n = 13) and a confirmed COVID-19 diagnosis. The patients were admitted to the hospital mainly through urgent or emergency care units.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Fagundes EM et al. Ann Hematol. 2021 Sep 17. doi:  10.1007/s00277-021-04659-w.

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first complete remission (CR1) after intensive chemotherapy (IC) offered clinical benefits in elderly patients with intermediate- or unfavorable-risk acute myeloid leukemia (AML).

Major finding: Patients who underwent allo-HSCT vs. those who did not had a significantly lower risk for relapse (hazard ratio [HR] 0.27), longer relapse-free survival (HR 0.47), and overall survival (HR 0.56), but a higher risk for nonrelapse mortality (HR 3.03; all P < .001).

Study details: This retrospective study included 507 elderly patients (age 60-70 years) with AML in CR1 after IC with intermediate or unfavorable risk cytogenetics, of which 203 patients underwent allo-HSCT.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Devillier R et al. Blood Adv. 2021 Sep 15. doi: 10.1182/bloodadvances.2021004435.

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first complete remission (CR1) after intensive chemotherapy (IC) offered clinical benefits in elderly patients with intermediate- or unfavorable-risk acute myeloid leukemia (AML).

Major finding: Patients who underwent allo-HSCT vs. those who did not had a significantly lower risk for relapse (hazard ratio [HR] 0.27), longer relapse-free survival (HR 0.47), and overall survival (HR 0.56), but a higher risk for nonrelapse mortality (HR 3.03; all P < .001).

Study details: This retrospective study included 507 elderly patients (age 60-70 years) with AML in CR1 after IC with intermediate or unfavorable risk cytogenetics, of which 203 patients underwent allo-HSCT.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Devillier R et al. Blood Adv. 2021 Sep 15. doi: 10.1182/bloodadvances.2021004435.

Key clinical point: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first complete remission (CR1) after intensive chemotherapy (IC) offered clinical benefits in elderly patients with intermediate- or unfavorable-risk acute myeloid leukemia (AML).

Major finding: Patients who underwent allo-HSCT vs. those who did not had a significantly lower risk for relapse (hazard ratio [HR] 0.27), longer relapse-free survival (HR 0.47), and overall survival (HR 0.56), but a higher risk for nonrelapse mortality (HR 3.03; all P < .001).

Study details: This retrospective study included 507 elderly patients (age 60-70 years) with AML in CR1 after IC with intermediate or unfavorable risk cytogenetics, of which 203 patients underwent allo-HSCT.

Disclosures: No source of funding was identified. The authors declared no conflict of interests.

Source: Devillier R et al. Blood Adv. 2021 Sep 15. doi: 10.1182/bloodadvances.2021004435.

Key clinical point: Patients with NPM1-mutant acute myeloid leukemia (AML) with NPM1-mutant measurable residual disease (MRD) positivity (MRD+) at the end of intensive chemotherapy (IC) and not undergoing hematopoietic stem cell transplant (HSCT) in the first remission had variable outcomes.

Major finding: At 12 months, 15% of patients had morphological relapse, 43% had molecular failure, 30% had complete molecular remission, and 12% had European LeukemiaNet-defined molecular persistence with a low copy number (MRD+ in complete remission).

Study details: This study included 100 patients with newly diagnosed NPM1-mutant AML who received at least 2 cycles of IC and had NPM1-mutant MRD+ at the end of IC and who did not plan to undergo HSCT in the first complete remission.

Disclosures: No specific source of funding was identified for this study. Some investigators, including the lead author, reported being on a speaker’s bureau and advisory boards for, receiving research funding and royalty payments from, or consulting for various pharmaceutical companies.

Source: Tiong IS et al. Blood Adv. 2021 Sep 23. doi: 10.1182/bloodadvances.2021005455.

Key clinical point: Patients with NPM1-mutant acute myeloid leukemia (AML) with NPM1-mutant measurable residual disease (MRD) positivity (MRD+) at the end of intensive chemotherapy (IC) and not undergoing hematopoietic stem cell transplant (HSCT) in the first remission had variable outcomes.

Major finding: At 12 months, 15% of patients had morphological relapse, 43% had molecular failure, 30% had complete molecular remission, and 12% had European LeukemiaNet-defined molecular persistence with a low copy number (MRD+ in complete remission).

Study details: This study included 100 patients with newly diagnosed NPM1-mutant AML who received at least 2 cycles of IC and had NPM1-mutant MRD+ at the end of IC and who did not plan to undergo HSCT in the first complete remission.

Disclosures: No specific source of funding was identified for this study. Some investigators, including the lead author, reported being on a speaker’s bureau and advisory boards for, receiving research funding and royalty payments from, or consulting for various pharmaceutical companies.

Source: Tiong IS et al. Blood Adv. 2021 Sep 23. doi: 10.1182/bloodadvances.2021005455.

Key clinical point: Patients with NPM1-mutant acute myeloid leukemia (AML) with NPM1-mutant measurable residual disease (MRD) positivity (MRD+) at the end of intensive chemotherapy (IC) and not undergoing hematopoietic stem cell transplant (HSCT) in the first remission had variable outcomes.

Major finding: At 12 months, 15% of patients had morphological relapse, 43% had molecular failure, 30% had complete molecular remission, and 12% had European LeukemiaNet-defined molecular persistence with a low copy number (MRD+ in complete remission).

Study details: This study included 100 patients with newly diagnosed NPM1-mutant AML who received at least 2 cycles of IC and had NPM1-mutant MRD+ at the end of IC and who did not plan to undergo HSCT in the first complete remission.

Disclosures: No specific source of funding was identified for this study. Some investigators, including the lead author, reported being on a speaker’s bureau and advisory boards for, receiving research funding and royalty payments from, or consulting for various pharmaceutical companies.

Source: Tiong IS et al. Blood Adv. 2021 Sep 23. doi: 10.1182/bloodadvances.2021005455.

Key clinical point: Combination of low-dose cytarabine (LDAC) with venetoclax vs. placebo improved survival and treatment response in treatment-naive patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC).

Major finding: LDAC+venetoclax vs. LDAC+placebo improved median overall survival (hazard ratio 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002).

Study details: This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).

Disclosures: This study was sponsored by AbbVie. Some investigators, including the lead author, reported receiving research and financial support from, being on advisory boards or boards of directors for, being a current or former employee of, holding stocks in, or receiving patents and royalties from various pharmaceutical companies, including AbbVie.

Source: Wei AH et al. Blood Cancer J. 2021;11:163. doi: 10.1038/s41408-021-00555-8.

Key clinical point: Combination of low-dose cytarabine (LDAC) with venetoclax vs. placebo improved survival and treatment response in treatment-naive patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC).

Major finding: LDAC+venetoclax vs. LDAC+placebo improved median overall survival (hazard ratio 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002).

Study details: This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).

Disclosures: This study was sponsored by AbbVie. Some investigators, including the lead author, reported receiving research and financial support from, being on advisory boards or boards of directors for, being a current or former employee of, holding stocks in, or receiving patents and royalties from various pharmaceutical companies, including AbbVie.

Source: Wei AH et al. Blood Cancer J. 2021;11:163. doi: 10.1038/s41408-021-00555-8.

Key clinical point: Combination of low-dose cytarabine (LDAC) with venetoclax vs. placebo improved survival and treatment response in treatment-naive patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC).

Major finding: LDAC+venetoclax vs. LDAC+placebo improved median overall survival (hazard ratio 0.70; P = .04), along with higher rates of complete response (CR) or CR with incomplete hematologic recovery (48.3% vs. 13.2%; P < .001) and postbaseline red blood cell and platelet transfusion independence (39.2% vs. 17.6%; P = .002).

Study details: This was a post hoc analysis performed after an additional 6 months of follow-up of the phase 3 VIALE-C trial, including 211 adult patients with AML who were treatment-naive and unsuitable for IC. Patients were randomly assigned to receive LDAC with venetoclax (n = 143) or placebo (n = 68).

Disclosures: This study was sponsored by AbbVie. Some investigators, including the lead author, reported receiving research and financial support from, being on advisory boards or boards of directors for, being a current or former employee of, holding stocks in, or receiving patents and royalties from various pharmaceutical companies, including AbbVie.

Source: Wei AH et al. Blood Cancer J. 2021;11:163. doi: 10.1038/s41408-021-00555-8.

Key clinical point: Salvage chemotherapy with a combination of fludarabine, cytarabine, granulocyte colony-stimulating factor, and mitoxantrone (Mito-FLAG) was effective and well-tolerated in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). However, consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is essential for long-term disease-free survival.

Major finding: Overall, 56.1% and 19.7% of patients achieved complete remission (CR) or CR with incomplete hematologic recovery and partial remission, respectively. The median overall survival (OS), 30-day mortality, and 60-day mortality were 13 (95% CI 10.2-15.8) months, 4.5%, and 7.6%, respectively. The median OS was superior in patients who underwent allo-HSCT (75.8%) vs. those who did not (17 months vs. 3 months; P < .001).

Study details: This retrospective study included 66 patients with R/R AML receiving Mito-FLAG treatment followed up for a median duration of 54 months.

Disclosures: This study did not receive any funding other than Open Access funding enabled and organized by Projekt DEAL. The authors declared no conflict of interests.

Source: Mühleck R et al. J Cancer Res Clin Oncol. 2021 Oct 5. doi: 10.1007/s00432-021-03821-1.

Key clinical point: Salvage chemotherapy with a combination of fludarabine, cytarabine, granulocyte colony-stimulating factor, and mitoxantrone (Mito-FLAG) was effective and well-tolerated in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). However, consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is essential for long-term disease-free survival.

Major finding: Overall, 56.1% and 19.7% of patients achieved complete remission (CR) or CR with incomplete hematologic recovery and partial remission, respectively. The median overall survival (OS), 30-day mortality, and 60-day mortality were 13 (95% CI 10.2-15.8) months, 4.5%, and 7.6%, respectively. The median OS was superior in patients who underwent allo-HSCT (75.8%) vs. those who did not (17 months vs. 3 months; P < .001).

Study details: This retrospective study included 66 patients with R/R AML receiving Mito-FLAG treatment followed up for a median duration of 54 months.

Disclosures: This study did not receive any funding other than Open Access funding enabled and organized by Projekt DEAL. The authors declared no conflict of interests.

Source: Mühleck R et al. J Cancer Res Clin Oncol. 2021 Oct 5. doi: 10.1007/s00432-021-03821-1.

Key clinical point: Salvage chemotherapy with a combination of fludarabine, cytarabine, granulocyte colony-stimulating factor, and mitoxantrone (Mito-FLAG) was effective and well-tolerated in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). However, consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is essential for long-term disease-free survival.

Major finding: Overall, 56.1% and 19.7% of patients achieved complete remission (CR) or CR with incomplete hematologic recovery and partial remission, respectively. The median overall survival (OS), 30-day mortality, and 60-day mortality were 13 (95% CI 10.2-15.8) months, 4.5%, and 7.6%, respectively. The median OS was superior in patients who underwent allo-HSCT (75.8%) vs. those who did not (17 months vs. 3 months; P < .001).

Study details: This retrospective study included 66 patients with R/R AML receiving Mito-FLAG treatment followed up for a median duration of 54 months.

Disclosures: This study did not receive any funding other than Open Access funding enabled and organized by Projekt DEAL. The authors declared no conflict of interests.

Source: Mühleck R et al. J Cancer Res Clin Oncol. 2021 Oct 5. doi: 10.1007/s00432-021-03821-1.

Key clinical point: Intensification of induction II chemotherapy with mitoxantrone and high-dose cytarabine (MA) did not improve survival, but increased toxicity in pediatric patients with high-risk acute myeloid leukemia (AML) vs. cytarabine/daunorubicin/etoposide (ADE).

Major finding: Induction II with MA vs. ADE did not improve 5-year disease-free survival (P = .632) and overall survival (P = .658). Fewer patients receiving MA vs. ADE achieved neutrophil (52.6% vs. 79.3%; P = .011) and platelet (60.0% vs. 82.8%; P = .024) recovery.

Study details: This study included 124 patients with newly diagnosed de novo high-risk AML treated in AAML0531 (n = 29) and AAML1031 (n = 95) trials. For induction II, patients in AAML0531 received ADE and those in AAML1031 received MA. Also, stem cell transplant conditioning used busulfan/cyclophosphamide in AAML0531 and busulfan/fludarabine along with liberalized donor eligibility in AAML1031 trials.

Disclosures: This study was supported by grants from the COG NCTN Network Group Operations Centres and NCTN Statistics and Data Center. M Loken and LE Brodersen reported being an employee of Hematologics Inc.

Source: Elgarten CW et al. Pediatr Blood Cancer. 2021 Oct 1. doi: 10.1002/pbc.29281.

Key clinical point: Intensification of induction II chemotherapy with mitoxantrone and high-dose cytarabine (MA) did not improve survival, but increased toxicity in pediatric patients with high-risk acute myeloid leukemia (AML) vs. cytarabine/daunorubicin/etoposide (ADE).

Major finding: Induction II with MA vs. ADE did not improve 5-year disease-free survival (P = .632) and overall survival (P = .658). Fewer patients receiving MA vs. ADE achieved neutrophil (52.6% vs. 79.3%; P = .011) and platelet (60.0% vs. 82.8%; P = .024) recovery.

Study details: This study included 124 patients with newly diagnosed de novo high-risk AML treated in AAML0531 (n = 29) and AAML1031 (n = 95) trials. For induction II, patients in AAML0531 received ADE and those in AAML1031 received MA. Also, stem cell transplant conditioning used busulfan/cyclophosphamide in AAML0531 and busulfan/fludarabine along with liberalized donor eligibility in AAML1031 trials.

Disclosures: This study was supported by grants from the COG NCTN Network Group Operations Centres and NCTN Statistics and Data Center. M Loken and LE Brodersen reported being an employee of Hematologics Inc.

Source: Elgarten CW et al. Pediatr Blood Cancer. 2021 Oct 1. doi: 10.1002/pbc.29281.

Key clinical point: Intensification of induction II chemotherapy with mitoxantrone and high-dose cytarabine (MA) did not improve survival, but increased toxicity in pediatric patients with high-risk acute myeloid leukemia (AML) vs. cytarabine/daunorubicin/etoposide (ADE).

Major finding: Induction II with MA vs. ADE did not improve 5-year disease-free survival (P = .632) and overall survival (P = .658). Fewer patients receiving MA vs. ADE achieved neutrophil (52.6% vs. 79.3%; P = .011) and platelet (60.0% vs. 82.8%; P = .024) recovery.

Study details: This study included 124 patients with newly diagnosed de novo high-risk AML treated in AAML0531 (n = 29) and AAML1031 (n = 95) trials. For induction II, patients in AAML0531 received ADE and those in AAML1031 received MA. Also, stem cell transplant conditioning used busulfan/cyclophosphamide in AAML0531 and busulfan/fludarabine along with liberalized donor eligibility in AAML1031 trials.

Disclosures: This study was supported by grants from the COG NCTN Network Group Operations Centres and NCTN Statistics and Data Center. M Loken and LE Brodersen reported being an employee of Hematologics Inc.

Source: Elgarten CW et al. Pediatr Blood Cancer. 2021 Oct 1. doi: 10.1002/pbc.29281.