AML

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.

Key clinical point: Enasidenib was associated with superior overall survival (OS) compared to standard of care (SoC) therapies in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation who were ineligible for hematopoietic stem cell transplantation (HSCT).

Major finding: Enasidenib vs. SoC was associated with a significantly longer OS (hazard ratio 0.67; 95% CI 0.47-0.97).

Study details: Findings are from a propensity score-matching analysis including adult patients with R/R AML with an IDH2 mutation ineligible for HSCT treated with enasidenib (n=195) from the AG221 C-001 trial or SoC therapies (n=78) from the French Chart Review study.

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

Source: de Botton S et al. Cancer Med. 2021 Aug 24. doi: 10.1002/cam4.4182.

Key clinical point: Enasidenib was associated with superior overall survival (OS) compared to standard of care (SoC) therapies in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation who were ineligible for hematopoietic stem cell transplantation (HSCT).

Major finding: Enasidenib vs. SoC was associated with a significantly longer OS (hazard ratio 0.67; 95% CI 0.47-0.97).

Study details: Findings are from a propensity score-matching analysis including adult patients with R/R AML with an IDH2 mutation ineligible for HSCT treated with enasidenib (n=195) from the AG221 C-001 trial or SoC therapies (n=78) from the French Chart Review study.

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

Source: de Botton S et al. Cancer Med. 2021 Aug 24. doi: 10.1002/cam4.4182.

Key clinical point: Enasidenib was associated with superior overall survival (OS) compared to standard of care (SoC) therapies in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation who were ineligible for hematopoietic stem cell transplantation (HSCT).

Major finding: Enasidenib vs. SoC was associated with a significantly longer OS (hazard ratio 0.67; 95% CI 0.47-0.97).

Study details: Findings are from a propensity score-matching analysis including adult patients with R/R AML with an IDH2 mutation ineligible for HSCT treated with enasidenib (n=195) from the AG221 C-001 trial or SoC therapies (n=78) from the French Chart Review study.

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

Source: de Botton S et al. Cancer Med. 2021 Aug 24. doi: 10.1002/cam4.4182.

Key clinical point: The administration of decitabine in alternating cycles with sapacitabine vs. decitabine monotherapy did not significantly improve outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) who were unfit or chose not to receive intensive induction chemotherapy.

Major finding: The median overall survival (5.9 months vs. 5.7 months; P = .8902) and rates of complete remission (16.6% vs. 10.8%; P = .1468) were not significantly different in patients receiving decitabine plus sapacitabine vs. decitabine monotherapy.

Study details: Findings are from the phase 3 SEAMLESS trial including 482 elderly patients (age, 70 years or older) with newly diagnosed AML unsuitable or unwilling for intensive induction chemotherapy. Patients were randomly assigned to receive either decitabine in alternating cycles with sapacitabine or decitabine monotherapy.

Disclosures: This study was sponsored by Cyclacel Limited (Dundee, Scotland, United Kingdom). The lead author reported research grants and honoraria from various sources. Other authors reported ties with various pharmaceutical companies including Cyclacel.

Source: Kantarjian HM et al. Cancer. 2021 Aug 23. doi: 10.1002/cncr.33828.

Key clinical point: The administration of decitabine in alternating cycles with sapacitabine vs. decitabine monotherapy did not significantly improve outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) who were unfit or chose not to receive intensive induction chemotherapy.

Major finding: The median overall survival (5.9 months vs. 5.7 months; P = .8902) and rates of complete remission (16.6% vs. 10.8%; P = .1468) were not significantly different in patients receiving decitabine plus sapacitabine vs. decitabine monotherapy.

Study details: Findings are from the phase 3 SEAMLESS trial including 482 elderly patients (age, 70 years or older) with newly diagnosed AML unsuitable or unwilling for intensive induction chemotherapy. Patients were randomly assigned to receive either decitabine in alternating cycles with sapacitabine or decitabine monotherapy.

Disclosures: This study was sponsored by Cyclacel Limited (Dundee, Scotland, United Kingdom). The lead author reported research grants and honoraria from various sources. Other authors reported ties with various pharmaceutical companies including Cyclacel.

Source: Kantarjian HM et al. Cancer. 2021 Aug 23. doi: 10.1002/cncr.33828.

Key clinical point: The administration of decitabine in alternating cycles with sapacitabine vs. decitabine monotherapy did not significantly improve outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) who were unfit or chose not to receive intensive induction chemotherapy.

Major finding: The median overall survival (5.9 months vs. 5.7 months; P = .8902) and rates of complete remission (16.6% vs. 10.8%; P = .1468) were not significantly different in patients receiving decitabine plus sapacitabine vs. decitabine monotherapy.

Study details: Findings are from the phase 3 SEAMLESS trial including 482 elderly patients (age, 70 years or older) with newly diagnosed AML unsuitable or unwilling for intensive induction chemotherapy. Patients were randomly assigned to receive either decitabine in alternating cycles with sapacitabine or decitabine monotherapy.

Disclosures: This study was sponsored by Cyclacel Limited (Dundee, Scotland, United Kingdom). The lead author reported research grants and honoraria from various sources. Other authors reported ties with various pharmaceutical companies including Cyclacel.

Source: Kantarjian HM et al. Cancer. 2021 Aug 23. doi: 10.1002/cncr.33828.

Of the 50 patients enrolled, 90%, 8% and 2% had newly diagnosed AML, myelodysplastic syndrome and mixed phenotype acute leukemia respectively. Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%). Only one patient had a p53 mutation and that patient did not respond.  Another study by Alwash et al, demonstrated that 15% of patients acquire a TP53 mutation during AML therapy.

The poor prognosis of patients with a p53 ,mutation was also seen in a retrospective study of patients with newly diagnosed or relapsed/refractory AML treated with 10-day decitabine + venetoclax (DEC10-VEN). Of the 118 patients, 35 had a TP53 mutation. Complete remission/complete remission with incomplete count recovery (57% vs 775), and overall response was better for patients without vs with a TP53 mutation. In addition, overall survival was dismal (5.2 months) for patients with TP53 mutation vs those without (19.4 months).

This study reiterates the need for newer therapies for this group of  patients with a TP53 mutation (Kim K et al). The overall outcome of patients treated with DEC10-VEN was  better compared to intensive chemotherapy (IC) in patients with relapsed refractory AML. This was evaluated in a retrospective study assessing the outcomes of adult patients with R/R AML treated with DEC10-VEN (n=65) a vs IC-based regimen (n=130) using propensity score-matched analysis. Patients receiving DEC10-VEN vs IC had superior overall response rate (odds ratio [OR], 3.28; P < .001), minimal residual disease negativity (OR, 2.48; P = .017), event-free survival (hazard ratio [HR], 0.46; P < .001), and overall survival (HR, 0.56; P = .008). Rates of refractory disease (OR, 0.46; P = .011) and 60-day mortality (OR, 0.40; P = .029) were significantly lower in patients receiving DEC10-VEN vs IC.

Of the 50 patients enrolled, 90%, 8% and 2% had newly diagnosed AML, myelodysplastic syndrome and mixed phenotype acute leukemia respectively. Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%). Only one patient had a p53 mutation and that patient did not respond.  Another study by Alwash et al, demonstrated that 15% of patients acquire a TP53 mutation during AML therapy.

The poor prognosis of patients with a p53 ,mutation was also seen in a retrospective study of patients with newly diagnosed or relapsed/refractory AML treated with 10-day decitabine + venetoclax (DEC10-VEN). Of the 118 patients, 35 had a TP53 mutation. Complete remission/complete remission with incomplete count recovery (57% vs 775), and overall response was better for patients without vs with a TP53 mutation. In addition, overall survival was dismal (5.2 months) for patients with TP53 mutation vs those without (19.4 months).

This study reiterates the need for newer therapies for this group of  patients with a TP53 mutation (Kim K et al). The overall outcome of patients treated with DEC10-VEN was  better compared to intensive chemotherapy (IC) in patients with relapsed refractory AML. This was evaluated in a retrospective study assessing the outcomes of adult patients with R/R AML treated with DEC10-VEN (n=65) a vs IC-based regimen (n=130) using propensity score-matched analysis. Patients receiving DEC10-VEN vs IC had superior overall response rate (odds ratio [OR], 3.28; P < .001), minimal residual disease negativity (OR, 2.48; P = .017), event-free survival (hazard ratio [HR], 0.46; P < .001), and overall survival (HR, 0.56; P = .008). Rates of refractory disease (OR, 0.46; P = .011) and 60-day mortality (OR, 0.40; P = .029) were significantly lower in patients receiving DEC10-VEN vs IC.

Of the 50 patients enrolled, 90%, 8% and 2% had newly diagnosed AML, myelodysplastic syndrome and mixed phenotype acute leukemia respectively. Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%). Only one patient had a p53 mutation and that patient did not respond.  Another study by Alwash et al, demonstrated that 15% of patients acquire a TP53 mutation during AML therapy.

The poor prognosis of patients with a p53 ,mutation was also seen in a retrospective study of patients with newly diagnosed or relapsed/refractory AML treated with 10-day decitabine + venetoclax (DEC10-VEN). Of the 118 patients, 35 had a TP53 mutation. Complete remission/complete remission with incomplete count recovery (57% vs 775), and overall response was better for patients without vs with a TP53 mutation. In addition, overall survival was dismal (5.2 months) for patients with TP53 mutation vs those without (19.4 months).

This study reiterates the need for newer therapies for this group of  patients with a TP53 mutation (Kim K et al). The overall outcome of patients treated with DEC10-VEN was  better compared to intensive chemotherapy (IC) in patients with relapsed refractory AML. This was evaluated in a retrospective study assessing the outcomes of adult patients with R/R AML treated with DEC10-VEN (n=65) a vs IC-based regimen (n=130) using propensity score-matched analysis. Patients receiving DEC10-VEN vs IC had superior overall response rate (odds ratio [OR], 3.28; P < .001), minimal residual disease negativity (OR, 2.48; P = .017), event-free survival (hazard ratio [HR], 0.46; P < .001), and overall survival (HR, 0.56; P = .008). Rates of refractory disease (OR, 0.46; P = .011) and 60-day mortality (OR, 0.40; P = .029) were significantly lower in patients receiving DEC10-VEN vs IC.

Key clinical point: Presence of SRSF2 mutations in patients with acute myeloid leukemia (AML) did not affect clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT).

Major finding: Overall, 12.5% of patients harbored an SRSF2 mutation that persisted in 93% of analyzed patients in remission prior to HSCT. SRSF2 P95 mutation at diagnosis and HSCT did not affect the cumulative incidence of relapse (both P = .68), event-free survival (P = .40 and P = .80, respectively), or overall survival (P = .10 and P = .90, respectively) in patients with AML consolidated with HSCT in complete remission (CR) or CR with incomplete peripheral recovery.

Study details: Findings are from a retrospective analysis of 263 adult patients with AML who underwent allogeneic HSCT between May 2000 and August 2020.

Disclosures: This work was supported by the Deutsche José-Carreras-Stiftung, Deutsche Gesellschaft für Innere Medizin, Verein zusammen gegen den Krebs e.V., and Ein Herz für Kinder e.V. The authors declared no conflict of interests.

Source: Grimm J et al. Am J Hematol. 2021 Jul 21. doi: 10.1002/ajh.26298.

Key clinical point: Presence of SRSF2 mutations in patients with acute myeloid leukemia (AML) did not affect clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT).

Major finding: Overall, 12.5% of patients harbored an SRSF2 mutation that persisted in 93% of analyzed patients in remission prior to HSCT. SRSF2 P95 mutation at diagnosis and HSCT did not affect the cumulative incidence of relapse (both P = .68), event-free survival (P = .40 and P = .80, respectively), or overall survival (P = .10 and P = .90, respectively) in patients with AML consolidated with HSCT in complete remission (CR) or CR with incomplete peripheral recovery.

Study details: Findings are from a retrospective analysis of 263 adult patients with AML who underwent allogeneic HSCT between May 2000 and August 2020.

Disclosures: This work was supported by the Deutsche José-Carreras-Stiftung, Deutsche Gesellschaft für Innere Medizin, Verein zusammen gegen den Krebs e.V., and Ein Herz für Kinder e.V. The authors declared no conflict of interests.

Source: Grimm J et al. Am J Hematol. 2021 Jul 21. doi: 10.1002/ajh.26298.

Key clinical point: Presence of SRSF2 mutations in patients with acute myeloid leukemia (AML) did not affect clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT).

Major finding: Overall, 12.5% of patients harbored an SRSF2 mutation that persisted in 93% of analyzed patients in remission prior to HSCT. SRSF2 P95 mutation at diagnosis and HSCT did not affect the cumulative incidence of relapse (both P = .68), event-free survival (P = .40 and P = .80, respectively), or overall survival (P = .10 and P = .90, respectively) in patients with AML consolidated with HSCT in complete remission (CR) or CR with incomplete peripheral recovery.

Study details: Findings are from a retrospective analysis of 263 adult patients with AML who underwent allogeneic HSCT between May 2000 and August 2020.

Disclosures: This work was supported by the Deutsche José-Carreras-Stiftung, Deutsche Gesellschaft für Innere Medizin, Verein zusammen gegen den Krebs e.V., and Ein Herz für Kinder e.V. The authors declared no conflict of interests.

Source: Grimm J et al. Am J Hematol. 2021 Jul 21. doi: 10.1002/ajh.26298.

Key clinical point: New tumor protein 53 (TP53) mutations could be acquired during acute myeloid leukemia (AML) treatment, particularly after intensive chemotherapy and hematopoietic stem cell transplantation (HSCT), in a proportion of patients with TP53 wild-type AML. Thus, sequential monitoring for emergent TP53 mutations during AML therapy may have clinical relevance.

Major finding: Overall, 15% of patients developed a newly detectable TP53 mutation during AML therapy, with a median variant allele frequency of 15%. Newly detected TP53 mutations were frequent in patients receiving intensive vs low-intensity chemotherapy (23% vs 10%; P = .02) and those who underwent HSCT vs those who did not (36% vs 12%; P = .005).

Study details: Findings are from a retrospective analysis of 200 adult patients with newly diagnosed TP53 wild-type AML who relapsed after or were refractory to frontline therapy.

Disclosures: This study was supported by MD Anderson Cancer Center Support Grant and SPORE. The authors declared no conflict of interests.

Source: Alwash Y et al. Am J Hematol. 2021 Aug 5. doi: 10.1002/ajh.26314.

Key clinical point: New tumor protein 53 (TP53) mutations could be acquired during acute myeloid leukemia (AML) treatment, particularly after intensive chemotherapy and hematopoietic stem cell transplantation (HSCT), in a proportion of patients with TP53 wild-type AML. Thus, sequential monitoring for emergent TP53 mutations during AML therapy may have clinical relevance.

Major finding: Overall, 15% of patients developed a newly detectable TP53 mutation during AML therapy, with a median variant allele frequency of 15%. Newly detected TP53 mutations were frequent in patients receiving intensive vs low-intensity chemotherapy (23% vs 10%; P = .02) and those who underwent HSCT vs those who did not (36% vs 12%; P = .005).

Study details: Findings are from a retrospective analysis of 200 adult patients with newly diagnosed TP53 wild-type AML who relapsed after or were refractory to frontline therapy.

Disclosures: This study was supported by MD Anderson Cancer Center Support Grant and SPORE. The authors declared no conflict of interests.

Source: Alwash Y et al. Am J Hematol. 2021 Aug 5. doi: 10.1002/ajh.26314.

Key clinical point: New tumor protein 53 (TP53) mutations could be acquired during acute myeloid leukemia (AML) treatment, particularly after intensive chemotherapy and hematopoietic stem cell transplantation (HSCT), in a proportion of patients with TP53 wild-type AML. Thus, sequential monitoring for emergent TP53 mutations during AML therapy may have clinical relevance.

Major finding: Overall, 15% of patients developed a newly detectable TP53 mutation during AML therapy, with a median variant allele frequency of 15%. Newly detected TP53 mutations were frequent in patients receiving intensive vs low-intensity chemotherapy (23% vs 10%; P = .02) and those who underwent HSCT vs those who did not (36% vs 12%; P = .005).

Study details: Findings are from a retrospective analysis of 200 adult patients with newly diagnosed TP53 wild-type AML who relapsed after or were refractory to frontline therapy.

Disclosures: This study was supported by MD Anderson Cancer Center Support Grant and SPORE. The authors declared no conflict of interests.

Source: Alwash Y et al. Am J Hematol. 2021 Aug 5. doi: 10.1002/ajh.26314.