AML

Key clinical point: Addition of quizartinib to low-dose ara-C (LDAC) vs. LDAC alone improved survival and response in older patients with acute myeloid leukemia (AML) with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC).

Major finding: 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 0.36; P = .024).

Study details: This 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.

Disclosures: This study was supported by UK National Institute for Health Research, Blood Cancer UK, and Daiichi Sankyo. Some investigators reported being on advisory boards for, receiving research funding and honoraria from, or being an employee of various pharmaceutical companies, including Daiichi Sankyo.

Source: Dennis M et al. Blood Adv. 2021 Oct 1. doi: 10.1182/bloodadvances.2021005038.

Key clinical point: Addition of quizartinib to low-dose ara-C (LDAC) vs. LDAC alone improved survival and response in older patients with acute myeloid leukemia (AML) with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC).

Major finding: 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 0.36; P = .024).

Study details: This 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.

Disclosures: This study was supported by UK National Institute for Health Research, Blood Cancer UK, and Daiichi Sankyo. Some investigators reported being on advisory boards for, receiving research funding and honoraria from, or being an employee of various pharmaceutical companies, including Daiichi Sankyo.

Source: Dennis M et al. Blood Adv. 2021 Oct 1. doi: 10.1182/bloodadvances.2021005038.

Key clinical point: Addition of quizartinib to low-dose ara-C (LDAC) vs. LDAC alone improved survival and response in older patients with acute myeloid leukemia (AML) with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation who were unfit for intensive chemotherapy (IC).

Major finding: 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 0.36; P = .024).

Study details: This 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.

Disclosures: This study was supported by UK National Institute for Health Research, Blood Cancer UK, and Daiichi Sankyo. Some investigators reported being on advisory boards for, receiving research funding and honoraria from, or being an employee of various pharmaceutical companies, including Daiichi Sankyo.

Source: Dennis M et al. Blood Adv. 2021 Oct 1. doi: 10.1182/bloodadvances.2021005038.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

Key clinical point: Among patients with acute myeloid leukemia (AML) who underwent first allogeneic hematopoietic stem cell transplantation (allo-HSCT), children showed superior clinical outcomes compared to adolescents and postadolescents (APA) and young adults.

Major finding: At 2 years, the cumulative incidence of chronic graft-versus-host disease (P < .0001), relapse (P = .0254), and nonrelapse mortality (P < .0001) were significantly lower, and overall survival (P = .0009) and event-free survival (P = .0186) were higher in children compared to APA and young adult patients with AML.

Study details: Findings are from a retrospective analysis of children (age 0-14 years; n = 564), APA patients (age 15-25 years; n = 647), and young adults (age 26-40 years; n = 1,434) with AML who received a first allo-HSCT in the first or further remission or in refractory state.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Pochon C et al. J Cancer Res Clin Oncol. 2021 Sep 4. doi: 10.1007/s00432-021-03761-w.

Key clinical point: Among patients with acute myeloid leukemia (AML) who underwent first allogeneic hematopoietic stem cell transplantation (allo-HSCT), children showed superior clinical outcomes compared to adolescents and postadolescents (APA) and young adults.

Major finding: At 2 years, the cumulative incidence of chronic graft-versus-host disease (P < .0001), relapse (P = .0254), and nonrelapse mortality (P < .0001) were significantly lower, and overall survival (P = .0009) and event-free survival (P = .0186) were higher in children compared to APA and young adult patients with AML.

Study details: Findings are from a retrospective analysis of children (age 0-14 years; n = 564), APA patients (age 15-25 years; n = 647), and young adults (age 26-40 years; n = 1,434) with AML who received a first allo-HSCT in the first or further remission or in refractory state.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Pochon C et al. J Cancer Res Clin Oncol. 2021 Sep 4. doi: 10.1007/s00432-021-03761-w.

Key clinical point: Among patients with acute myeloid leukemia (AML) who underwent first allogeneic hematopoietic stem cell transplantation (allo-HSCT), children showed superior clinical outcomes compared to adolescents and postadolescents (APA) and young adults.

Major finding: At 2 years, the cumulative incidence of chronic graft-versus-host disease (P < .0001), relapse (P = .0254), and nonrelapse mortality (P < .0001) were significantly lower, and overall survival (P = .0009) and event-free survival (P = .0186) were higher in children compared to APA and young adult patients with AML.

Study details: Findings are from a retrospective analysis of children (age 0-14 years; n = 564), APA patients (age 15-25 years; n = 647), and young adults (age 26-40 years; n = 1,434) with AML who received a first allo-HSCT in the first or further remission or in refractory state.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Pochon C et al. J Cancer Res Clin Oncol. 2021 Sep 4. doi: 10.1007/s00432-021-03761-w.

Key clinical point: The maximum tolerated dose (MTD) of combined romidepsin and azacitidine (ROM/AZA) therapy was well tolerated and clinically active in patients with newly diagnosed, relapsed or refractory (R/R) acute myeloid leukemia (AML) and unfit for intensive chemotherapy.

Major finding: Overall, 23.7% of patients treated with the MTD had a complete remission (CR)/incomplete CR or partial response by cycle 6. The combination therapy was well tolerated with 5 grade 3 or higher nonhematologic treatment-related adverse events affecting at least 10% of patients. Only 4 patients discontinued treatment because of toxicity.

Study details: Findings are from the phase 1/2 ROMAZA trial including 48 patients with newly diagnosed, R/R AML ineligible for intensive chemotherapy. The MTD of ROM/AZA therapy was established as 12 mg/m² romidepcin on days 8 and 15 with 75 mg/m² azacitidine on days 1-9.

Disclosures: This study was funded by Bloodwise and Celgene. The lead author reported ties with Novartis, Daichi-Sankyo, Pfizer, Janssen, and Amgen. Some investigators reported ties with various pharmaceutical companies, including Celgene.

Source: Loke J et al. Br J Haematol. 2021 Sep 6. doi: 10.1111/bjh.17823.

Key clinical point: The maximum tolerated dose (MTD) of combined romidepsin and azacitidine (ROM/AZA) therapy was well tolerated and clinically active in patients with newly diagnosed, relapsed or refractory (R/R) acute myeloid leukemia (AML) and unfit for intensive chemotherapy.

Major finding: Overall, 23.7% of patients treated with the MTD had a complete remission (CR)/incomplete CR or partial response by cycle 6. The combination therapy was well tolerated with 5 grade 3 or higher nonhematologic treatment-related adverse events affecting at least 10% of patients. Only 4 patients discontinued treatment because of toxicity.

Study details: Findings are from the phase 1/2 ROMAZA trial including 48 patients with newly diagnosed, R/R AML ineligible for intensive chemotherapy. The MTD of ROM/AZA therapy was established as 12 mg/m² romidepcin on days 8 and 15 with 75 mg/m² azacitidine on days 1-9.

Disclosures: This study was funded by Bloodwise and Celgene. The lead author reported ties with Novartis, Daichi-Sankyo, Pfizer, Janssen, and Amgen. Some investigators reported ties with various pharmaceutical companies, including Celgene.

Source: Loke J et al. Br J Haematol. 2021 Sep 6. doi: 10.1111/bjh.17823.

Key clinical point: The maximum tolerated dose (MTD) of combined romidepsin and azacitidine (ROM/AZA) therapy was well tolerated and clinically active in patients with newly diagnosed, relapsed or refractory (R/R) acute myeloid leukemia (AML) and unfit for intensive chemotherapy.

Major finding: Overall, 23.7% of patients treated with the MTD had a complete remission (CR)/incomplete CR or partial response by cycle 6. The combination therapy was well tolerated with 5 grade 3 or higher nonhematologic treatment-related adverse events affecting at least 10% of patients. Only 4 patients discontinued treatment because of toxicity.

Study details: Findings are from the phase 1/2 ROMAZA trial including 48 patients with newly diagnosed, R/R AML ineligible for intensive chemotherapy. The MTD of ROM/AZA therapy was established as 12 mg/m² romidepcin on days 8 and 15 with 75 mg/m² azacitidine on days 1-9.

Disclosures: This study was funded by Bloodwise and Celgene. The lead author reported ties with Novartis, Daichi-Sankyo, Pfizer, Janssen, and Amgen. Some investigators reported ties with various pharmaceutical companies, including Celgene.

Source: Loke J et al. Br J Haematol. 2021 Sep 6. doi: 10.1111/bjh.17823.

Key clinical point: Patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their first complete remission (CR) from a mismatched unrelated donor (MMUD), umbilical cord blood (UCB), or a haploidentical-related donor (Haplo) had similar outcomes, making all of them a viable option in the absence of a matched related or unrelated donor.

Major finding: For patients who had transplants between 2015 and 2018, the 3-year overall survival of MMUD, UCB, and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-versus-host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups.

Study details: Findings are from a retrospective analysis of 1,932 patients with AML who underwent allo-HSCT during their first CR from MMUD, UCB or Haplo.

Disclosures: This study was supported by grants from the Practical Research Project for Allergic Diseases and Immunology from the Japan Agency for Medical Research and Development and the Aichi Cancer Research Foundation. The authors declared no conflicts of interest.

Source: Yanada M et al. Transplant Cell Ther. 2021 Sep 6. doi: 10.1016/j.jtct.2021.08.027.

Key clinical point: Patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their first complete remission (CR) from a mismatched unrelated donor (MMUD), umbilical cord blood (UCB), or a haploidentical-related donor (Haplo) had similar outcomes, making all of them a viable option in the absence of a matched related or unrelated donor.

Major finding: For patients who had transplants between 2015 and 2018, the 3-year overall survival of MMUD, UCB, and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-versus-host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups.

Study details: Findings are from a retrospective analysis of 1,932 patients with AML who underwent allo-HSCT during their first CR from MMUD, UCB or Haplo.

Disclosures: This study was supported by grants from the Practical Research Project for Allergic Diseases and Immunology from the Japan Agency for Medical Research and Development and the Aichi Cancer Research Foundation. The authors declared no conflicts of interest.

Source: Yanada M et al. Transplant Cell Ther. 2021 Sep 6. doi: 10.1016/j.jtct.2021.08.027.

Key clinical point: Patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their first complete remission (CR) from a mismatched unrelated donor (MMUD), umbilical cord blood (UCB), or a haploidentical-related donor (Haplo) had similar outcomes, making all of them a viable option in the absence of a matched related or unrelated donor.

Major finding: For patients who had transplants between 2015 and 2018, the 3-year overall survival of MMUD, UCB, and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-versus-host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups.

Study details: Findings are from a retrospective analysis of 1,932 patients with AML who underwent allo-HSCT during their first CR from MMUD, UCB or Haplo.

Disclosures: This study was supported by grants from the Practical Research Project for Allergic Diseases and Immunology from the Japan Agency for Medical Research and Development and the Aichi Cancer Research Foundation. The authors declared no conflicts of interest.

Source: Yanada M et al. Transplant Cell Ther. 2021 Sep 6. doi: 10.1016/j.jtct.2021.08.027.

Key clinical point: De-escalation of cytarabine exposure by elimination of the fifth chemotherapy course should only be considered in pediatric patients with low-risk acute myeloid leukemia (LR-AML) with favorable cytogenetic/molecular features and negative minimal residual disease (MRD) at the end of first induction (EOI1).

Major finding: Overall, patients who received 4 vs. 5 chemotherapy courses had worse disease-free survival (DFS; hazard ratio [HR] 1.45; P = .009) and relapse risk (HR 1.40; P = .019). However, patients with favorable cytogenetic/molecular features and negative MRD at EOI1 had no difference in DFS (P = .934) and overall survival (P = .928) with 4 vs. 5 chemotherapy courses.

Study details: This prospective study assessed 923 pediatric patients with LR-AML treated in either AAML0531 (n = 225; excluding those treated with gemtuzumab ozogamicin) or AAML1031 (n = 698) trials with 4 (79%) or 5 (21%) courses of frontline chemotherapy.

Disclosures: This study was supported by National Clinical Trials Network (NCTN) Operations Center, NCTN Statistics & Data Center, St. Baldrick’s Foundation, Alex’s Lemonade Stand Foundation, and National Heart Lung and Blood Institute. The authors declared no conflicts of interest.

Source: Getz KD et al. Pediatr Blood Cancer. 2021 Sep 2. doi: 10.1002/pbc.29313.

Key clinical point: De-escalation of cytarabine exposure by elimination of the fifth chemotherapy course should only be considered in pediatric patients with low-risk acute myeloid leukemia (LR-AML) with favorable cytogenetic/molecular features and negative minimal residual disease (MRD) at the end of first induction (EOI1).

Major finding: Overall, patients who received 4 vs. 5 chemotherapy courses had worse disease-free survival (DFS; hazard ratio [HR] 1.45; P = .009) and relapse risk (HR 1.40; P = .019). However, patients with favorable cytogenetic/molecular features and negative MRD at EOI1 had no difference in DFS (P = .934) and overall survival (P = .928) with 4 vs. 5 chemotherapy courses.

Study details: This prospective study assessed 923 pediatric patients with LR-AML treated in either AAML0531 (n = 225; excluding those treated with gemtuzumab ozogamicin) or AAML1031 (n = 698) trials with 4 (79%) or 5 (21%) courses of frontline chemotherapy.

Disclosures: This study was supported by National Clinical Trials Network (NCTN) Operations Center, NCTN Statistics & Data Center, St. Baldrick’s Foundation, Alex’s Lemonade Stand Foundation, and National Heart Lung and Blood Institute. The authors declared no conflicts of interest.

Source: Getz KD et al. Pediatr Blood Cancer. 2021 Sep 2. doi: 10.1002/pbc.29313.

Key clinical point: De-escalation of cytarabine exposure by elimination of the fifth chemotherapy course should only be considered in pediatric patients with low-risk acute myeloid leukemia (LR-AML) with favorable cytogenetic/molecular features and negative minimal residual disease (MRD) at the end of first induction (EOI1).

Major finding: Overall, patients who received 4 vs. 5 chemotherapy courses had worse disease-free survival (DFS; hazard ratio [HR] 1.45; P = .009) and relapse risk (HR 1.40; P = .019). However, patients with favorable cytogenetic/molecular features and negative MRD at EOI1 had no difference in DFS (P = .934) and overall survival (P = .928) with 4 vs. 5 chemotherapy courses.

Study details: This prospective study assessed 923 pediatric patients with LR-AML treated in either AAML0531 (n = 225; excluding those treated with gemtuzumab ozogamicin) or AAML1031 (n = 698) trials with 4 (79%) or 5 (21%) courses of frontline chemotherapy.

Disclosures: This study was supported by National Clinical Trials Network (NCTN) Operations Center, NCTN Statistics & Data Center, St. Baldrick’s Foundation, Alex’s Lemonade Stand Foundation, and National Heart Lung and Blood Institute. The authors declared no conflicts of interest.

Source: Getz KD et al. Pediatr Blood Cancer. 2021 Sep 2. doi: 10.1002/pbc.29313.

Key clinical point: Mutations of the CCAAT/enhancer-binding protein alpha gene (CEBPA) in the basic leucine zipper domain (bZIP), even when detected as single-mutated CEBPA, were associated with favorable prognosis in patients with de novo acute myeloid leukemia (AML).

Major finding: Patients with compared to without CEBPA mutation in bZIP had a higher rate of complete remission, longer overall survival (OS), and lower cumulative incidence of relapse (all P < .001). Among patients with single-mutated CEBPA, those with CEBPA mutation in compared to out-of bZIP had a significantly longer OS (P = .008).

Study details: Findings are from a retrospective analysis of 1,028 patients with de novo AML.

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

Source: Wakita S et al. Blood Adv. 2021 Aug 27. doi: 10.1182/bloodadvances.2021004292.

Key clinical point: Mutations of the CCAAT/enhancer-binding protein alpha gene (CEBPA) in the basic leucine zipper domain (bZIP), even when detected as single-mutated CEBPA, were associated with favorable prognosis in patients with de novo acute myeloid leukemia (AML).

Major finding: Patients with compared to without CEBPA mutation in bZIP had a higher rate of complete remission, longer overall survival (OS), and lower cumulative incidence of relapse (all P < .001). Among patients with single-mutated CEBPA, those with CEBPA mutation in compared to out-of bZIP had a significantly longer OS (P = .008).

Study details: Findings are from a retrospective analysis of 1,028 patients with de novo AML.

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

Source: Wakita S et al. Blood Adv. 2021 Aug 27. doi: 10.1182/bloodadvances.2021004292.

Key clinical point: Mutations of the CCAAT/enhancer-binding protein alpha gene (CEBPA) in the basic leucine zipper domain (bZIP), even when detected as single-mutated CEBPA, were associated with favorable prognosis in patients with de novo acute myeloid leukemia (AML).

Major finding: Patients with compared to without CEBPA mutation in bZIP had a higher rate of complete remission, longer overall survival (OS), and lower cumulative incidence of relapse (all P < .001). Among patients with single-mutated CEBPA, those with CEBPA mutation in compared to out-of bZIP had a significantly longer OS (P = .008).

Study details: Findings are from a retrospective analysis of 1,028 patients with de novo AML.

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

Source: Wakita S et al. Blood Adv. 2021 Aug 27. doi: 10.1182/bloodadvances.2021004292.

Key clinical point: Oral azacitidine (OA) maintenance had a manageable safety profile in patients with newly diagnosed acute myeloid leukemia (AML) who attained the first complete remission (CR) or CR with incomplete blood count recovery (CRi) after induction chemotherapy (IC). However, blood count monitoring for at least the first 2 treatment cycles is recommended.

Major finding: Gastrointestinal (91% vs. 62%) and hematologic (66% vs. 47%) adverse events were common with OA vs. placebo. Adverse events were mostly manageable with dose interruptions (43%) or reductions (16%) and infrequently led to OA discontinuation (13%).

Study details: This safety analysis of the QUAZAR AML-001 trial included 469 patients with newly diagnosed AML with intermediate- or poor-risk cytogenetics who attained the first CR/CRi after IC, randomly assigned to receive either 300 mg OA (n = 236) or placebo (n = 233).

Disclosures: This study was funded by Celgene, a Bristol Myers Squibb Company. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Celgene and Bristol Myers Squibb.

Source: Ravandi F et al. J Hematol Oncol. 2021 Aug 28. doi: 10.1186/s13045-021-01142-x.

Key clinical point: Oral azacitidine (OA) maintenance had a manageable safety profile in patients with newly diagnosed acute myeloid leukemia (AML) who attained the first complete remission (CR) or CR with incomplete blood count recovery (CRi) after induction chemotherapy (IC). However, blood count monitoring for at least the first 2 treatment cycles is recommended.

Major finding: Gastrointestinal (91% vs. 62%) and hematologic (66% vs. 47%) adverse events were common with OA vs. placebo. Adverse events were mostly manageable with dose interruptions (43%) or reductions (16%) and infrequently led to OA discontinuation (13%).

Study details: This safety analysis of the QUAZAR AML-001 trial included 469 patients with newly diagnosed AML with intermediate- or poor-risk cytogenetics who attained the first CR/CRi after IC, randomly assigned to receive either 300 mg OA (n = 236) or placebo (n = 233).

Disclosures: This study was funded by Celgene, a Bristol Myers Squibb Company. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Celgene and Bristol Myers Squibb.

Source: Ravandi F et al. J Hematol Oncol. 2021 Aug 28. doi: 10.1186/s13045-021-01142-x.

Key clinical point: Oral azacitidine (OA) maintenance had a manageable safety profile in patients with newly diagnosed acute myeloid leukemia (AML) who attained the first complete remission (CR) or CR with incomplete blood count recovery (CRi) after induction chemotherapy (IC). However, blood count monitoring for at least the first 2 treatment cycles is recommended.

Major finding: Gastrointestinal (91% vs. 62%) and hematologic (66% vs. 47%) adverse events were common with OA vs. placebo. Adverse events were mostly manageable with dose interruptions (43%) or reductions (16%) and infrequently led to OA discontinuation (13%).

Study details: This safety analysis of the QUAZAR AML-001 trial included 469 patients with newly diagnosed AML with intermediate- or poor-risk cytogenetics who attained the first CR/CRi after IC, randomly assigned to receive either 300 mg OA (n = 236) or placebo (n = 233).

Disclosures: This study was funded by Celgene, a Bristol Myers Squibb Company. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Celgene and Bristol Myers Squibb.

Source: Ravandi F et al. J Hematol Oncol. 2021 Aug 28. doi: 10.1186/s13045-021-01142-x.

Key clinical point: Low-intensity treatment with low-dose cytarabine (LD-AC) combined with cladribine offered therapeutic benefit with an acceptable safety profile in elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy.

Major finding: Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (hazard ratio [HR] 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

Study details: Findings are from a prospective analysis of 117 elderly patients (age, 60 years or older) with AML with poor performance status or a high comorbidity index treated with frontline LD-AC and cladribine.

Disclosures: This study was supported by the Institute of Hematology and Transfusion Medicine in Warsaw and Polish Adult Leukemia Group. The authors declared no conflicts of interest.

Source: Budziszewska BK et al. Cancers. 2021 Aug 20. doi: 10.3390/cancers13164189.

Key clinical point: Low-intensity treatment with low-dose cytarabine (LD-AC) combined with cladribine offered therapeutic benefit with an acceptable safety profile in elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy.

Major finding: Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (hazard ratio [HR] 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

Study details: Findings are from a prospective analysis of 117 elderly patients (age, 60 years or older) with AML with poor performance status or a high comorbidity index treated with frontline LD-AC and cladribine.

Disclosures: This study was supported by the Institute of Hematology and Transfusion Medicine in Warsaw and Polish Adult Leukemia Group. The authors declared no conflicts of interest.

Source: Budziszewska BK et al. Cancers. 2021 Aug 20. doi: 10.3390/cancers13164189.

Key clinical point: Low-intensity treatment with low-dose cytarabine (LD-AC) combined with cladribine offered therapeutic benefit with an acceptable safety profile in elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy.

Major finding: Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (hazard ratio [HR] 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

Study details: Findings are from a prospective analysis of 117 elderly patients (age, 60 years or older) with AML with poor performance status or a high comorbidity index treated with frontline LD-AC and cladribine.

Disclosures: This study was supported by the Institute of Hematology and Transfusion Medicine in Warsaw and Polish Adult Leukemia Group. The authors declared no conflicts of interest.

Source: Budziszewska BK et al. Cancers. 2021 Aug 20. doi: 10.3390/cancers13164189.

Key clinical point: Gemtuzumab ozogamicin (GO) showed superior survival outcomes in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) than non-GO therapy, but higher dose increased the risk for early death.

Major finding: GO vs. non-GO arm showed improved overall survival (hazard ratio [HR], 0.86; P = .003), event-free survival (HR, 0.86; P = .015), and relapse-free survival (HR, 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of 6 mg/m² or higher (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018).

Study details: Findings are from a meta-analysis of 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk MDS (n = 129).

Disclosures: This study was supported by the Chinese National Major Project for New Drug Innovation, the National Natural Science Foundation of China, Shenzhen Science and Technology Foundation, and Shenzhen Key Laboratory Foundation. The authors declared no conflicts of interest.

Source: Xu Q et al. Front Immunol. 2021 Aug 16. doi: 10.3389/fimmu.2021.683595.

Key clinical point: Gemtuzumab ozogamicin (GO) showed superior survival outcomes in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) than non-GO therapy, but higher dose increased the risk for early death.

Major finding: GO vs. non-GO arm showed improved overall survival (hazard ratio [HR], 0.86; P = .003), event-free survival (HR, 0.86; P = .015), and relapse-free survival (HR, 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of 6 mg/m² or higher (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018).

Study details: Findings are from a meta-analysis of 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk MDS (n = 129).

Disclosures: This study was supported by the Chinese National Major Project for New Drug Innovation, the National Natural Science Foundation of China, Shenzhen Science and Technology Foundation, and Shenzhen Key Laboratory Foundation. The authors declared no conflicts of interest.

Source: Xu Q et al. Front Immunol. 2021 Aug 16. doi: 10.3389/fimmu.2021.683595.

Key clinical point: Gemtuzumab ozogamicin (GO) showed superior survival outcomes in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) than non-GO therapy, but higher dose increased the risk for early death.

Major finding: GO vs. non-GO arm showed improved overall survival (hazard ratio [HR], 0.86; P = .003), event-free survival (HR, 0.86; P = .015), and relapse-free survival (HR, 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of 6 mg/m² or higher (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018).

Study details: Findings are from a meta-analysis of 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk MDS (n = 129).

Disclosures: This study was supported by the Chinese National Major Project for New Drug Innovation, the National Natural Science Foundation of China, Shenzhen Science and Technology Foundation, and Shenzhen Key Laboratory Foundation. The authors declared no conflicts of interest.

Source: Xu Q et al. Front Immunol. 2021 Aug 16. doi: 10.3389/fimmu.2021.683595.