Clinical Edge Journal Scan Commentary: AML December 2021

This month, the phase II randomized study of azacitidine vs. azacitidine + enasidenib was reported by Dinardo et al.¹ The primary endpoint was overall response rate. The study included 101 adult patients with newly diagnosed mutant-IDH2 acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. They were randomly assigned to enasidenib and azacitidine (Ena-AZA, n = 68) or azacitidine alone (AZA, n = 33). The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). More importantly, the rates of complete remission/complete remission with partial hematologic recovery was higher with Ena-AZA vs. AZA (57% vs. 18% P = .0001). The duration of response was 24.1 months vs 9.9 months for the Ena-AZA vs AZA group. Despite the higher and more durable responses with Ena+AZA, there was no difference in overall survival. The authors attributed that to patients receiving other effective therapies after disease progression. Overall patients tolerated the combination therapy well. The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).  

Another study from the NCRI AML 16 trial demonstrated that reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with AML who lacked favorable risk cytogenetics and were considered fit for intensive treatment. During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001). The trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

The outcome of patients with AML and central nervous system (CNS) involvement at presentation was reported by Ganzel et al. In that study, the investigators evaluated the incidence of CNS involvement in 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials. The incidence of CNS incolvement was 1.111 % (36 of 3240 patients). CNS involvement had no effect on remission rates or survival.

References

1. Dinardo CD et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021;22(11):P1597-1608 (Nov 1).
2. Russell NH et al. Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial. Haematologica. 2021(Oct 14).
3. Ganzel C et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021(Nov 12);5(22):4560-4568. doi: 10.1182/bloodadvances.2021004999.

This month, the phase II randomized study of azacitidine vs. azacitidine + enasidenib was reported by Dinardo et al.¹ The primary endpoint was overall response rate. The study included 101 adult patients with newly diagnosed mutant-IDH2 acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. They were randomly assigned to enasidenib and azacitidine (Ena-AZA, n = 68) or azacitidine alone (AZA, n = 33). The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). More importantly, the rates of complete remission/complete remission with partial hematologic recovery was higher with Ena-AZA vs. AZA (57% vs. 18% P = .0001). The duration of response was 24.1 months vs 9.9 months for the Ena-AZA vs AZA group. Despite the higher and more durable responses with Ena+AZA, there was no difference in overall survival. The authors attributed that to patients receiving other effective therapies after disease progression. Overall patients tolerated the combination therapy well. The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).  

Another study from the NCRI AML 16 trial demonstrated that reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with AML who lacked favorable risk cytogenetics and were considered fit for intensive treatment. During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001). The trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

The outcome of patients with AML and central nervous system (CNS) involvement at presentation was reported by Ganzel et al. In that study, the investigators evaluated the incidence of CNS involvement in 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials. The incidence of CNS incolvement was 1.111 % (36 of 3240 patients). CNS involvement had no effect on remission rates or survival.

References

1. Dinardo CD et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021;22(11):P1597-1608 (Nov 1).
2. Russell NH et al. Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial. Haematologica. 2021(Oct 14).
3. Ganzel C et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021(Nov 12);5(22):4560-4568. doi: 10.1182/bloodadvances.2021004999.

This month, the phase II randomized study of azacitidine vs. azacitidine + enasidenib was reported by Dinardo et al.¹ The primary endpoint was overall response rate. The study included 101 adult patients with newly diagnosed mutant-IDH2 acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. They were randomly assigned to enasidenib and azacitidine (Ena-AZA, n = 68) or azacitidine alone (AZA, n = 33). The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). More importantly, the rates of complete remission/complete remission with partial hematologic recovery was higher with Ena-AZA vs. AZA (57% vs. 18% P = .0001). The duration of response was 24.1 months vs 9.9 months for the Ena-AZA vs AZA group. Despite the higher and more durable responses with Ena+AZA, there was no difference in overall survival. The authors attributed that to patients receiving other effective therapies after disease progression. Overall patients tolerated the combination therapy well. The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).  

Another study from the NCRI AML 16 trial demonstrated that reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with AML who lacked favorable risk cytogenetics and were considered fit for intensive treatment. During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001). The trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

The outcome of patients with AML and central nervous system (CNS) involvement at presentation was reported by Ganzel et al. In that study, the investigators evaluated the incidence of CNS involvement in 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials. The incidence of CNS incolvement was 1.111 % (36 of 3240 patients). CNS involvement had no effect on remission rates or survival.

References

1. Dinardo CD et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021;22(11):P1597-1608 (Nov 1).
2. Russell NH et al. Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial. Haematologica. 2021(Oct 14).
3. Ganzel C et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021(Nov 12);5(22):4560-4568. doi: 10.1182/bloodadvances.2021004999.