AML

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.

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.