Contributions
Abstract: EP488
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Intensive induction chemotherapy is the standard approach in patients (pts) with acute myeloid leukaemia (AML) for achieving complete remission (CR), enabling the delivery of consolidation treatment. Since achievement of CR is a strong predictor of survival, it is important to optimize the induction chemotherapy protocol.
Aims
Comparison induction regimen for AML with standard-dose 7+3 versus 10+3+etoposide.
Methods
Unicentric retrospective review of pts diagnosed with AML (excluding M3) from January 2012 to June 2020 treated with standard-dose 7+3 (cytarabine 200mg/m2 day 1-7 + daunorubicin 60mg/m2 day 1-3) and 10+3+E (cytarabine 100mg/m2 day 1-10 + daunorubicin 50mg/m2 day 1, 3, 5 + etoposide 50mg/m2 day 1-5).
Results
Identified 173 pts - median age 50 years (19-70y), 53% women. Secondary AML was diagnosed in 18.5% and according to the European Leukemia Net (ELN) risk stratification 38% had favourable risk, 43% intermediate and 19% unfavourable. Median leukocyte at diagnosis was 10.56x109/L and bone marrow blast 52%. Age (median 53y in 7+3 vs 48y in 10+3+E; p<0.001) was the only characteristic that differed between treatment (tt) arms.
From the pts identified, 61 received 7+3 and 112 received 10+3+E. A total of 78% achieved CR after one cycle of induction tt – 77% in 7+3 vs 78.6% in 10+3+E, without statistically significant difference (p=0.817). Only ELN risk had statistical impact on CR - 94% in favourable vs 77% in intermediate vs 48% in unfavourable (p<0.001). Partial remission and refractory disease were both obtained in 8%, without statistically significant difference. 10 pts died before evaluation of response, all of them as a consequence of bone marrow aplasia, with no difference between tt arms.
Median neutrophil-recovery time was different between tt [27days (10-74d) in 7+3 vs 31days (10-65d) in 10+3+E; p=0.02]. Median myelosuppression-recovery time (Hb>8g/dL; Leuk>1.5x109/L; Plaq>20x109/L) wasn’t statistically significant between tt (median 28days in 7+3 vs 30days in 10+3+E; p=0.216). Also the number of febrile neutropenia wasn’t different, with a median 2 episodes/patient. 16 pts required ICU admission, with no difference between tt.
Early relapse rate (≤6 months after induction tt) was 6.4%, lower in 10+3+E arm (3.6% vs 11.5%; p=0.047), regardless ELN risk. Overall relapse rate was 47% with statistically difference according to ELN risk (61% vs 50% vs 38% in unfavourable, intermediate and favourable risk; p<0.001) but no difference by tt arm (p=0.296). Median overall survival (OS) was 20months (95%CI 16-24months), without difference by tt (p=0.651).
At univariate analysis, several factors were associated with poor OS: ELN risk (p<0.001; HR 2.166), myelosuppression ≥50days (p=0.005; HR 18.717), neutropenia ≥60days (p<0.001; HR 17.711), ICU admission (p<0.001; HR 3.152) and disease relapse (p<0.001; HR 1.029). CR after induction was a protective factor (p<0.001; HR 0.389). At multivariate analysis factors that remained significant were: ELN risk (p<0.033; HR 2.148), myelosuppression ≥50days (p=0.003; HR 5.302), ICU admission (p=0.015; HR 2.706) and disease relapse (p<0.001; HR 13.937).
Conclusion
Outcomes were similar, with both induction regimens increased CR rates without increasing mortality in patients with AML fit for intensive treatment.
The only identified difference was that addiction of etoposide to 7+3 regimen had a lower early relapse rate but with slightly increased haematological toxicity. No difference was observed in overall relapse rate.
Thus, both induction regimens are effective and tolerated in fit adult patients with AML.
Keyword(s): Acute myeloid leukemia, Induction chemotherapy
Abstract: EP488
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
Intensive induction chemotherapy is the standard approach in patients (pts) with acute myeloid leukaemia (AML) for achieving complete remission (CR), enabling the delivery of consolidation treatment. Since achievement of CR is a strong predictor of survival, it is important to optimize the induction chemotherapy protocol.
Aims
Comparison induction regimen for AML with standard-dose 7+3 versus 10+3+etoposide.
Methods
Unicentric retrospective review of pts diagnosed with AML (excluding M3) from January 2012 to June 2020 treated with standard-dose 7+3 (cytarabine 200mg/m2 day 1-7 + daunorubicin 60mg/m2 day 1-3) and 10+3+E (cytarabine 100mg/m2 day 1-10 + daunorubicin 50mg/m2 day 1, 3, 5 + etoposide 50mg/m2 day 1-5).
Results
Identified 173 pts - median age 50 years (19-70y), 53% women. Secondary AML was diagnosed in 18.5% and according to the European Leukemia Net (ELN) risk stratification 38% had favourable risk, 43% intermediate and 19% unfavourable. Median leukocyte at diagnosis was 10.56x109/L and bone marrow blast 52%. Age (median 53y in 7+3 vs 48y in 10+3+E; p<0.001) was the only characteristic that differed between treatment (tt) arms.
From the pts identified, 61 received 7+3 and 112 received 10+3+E. A total of 78% achieved CR after one cycle of induction tt – 77% in 7+3 vs 78.6% in 10+3+E, without statistically significant difference (p=0.817). Only ELN risk had statistical impact on CR - 94% in favourable vs 77% in intermediate vs 48% in unfavourable (p<0.001). Partial remission and refractory disease were both obtained in 8%, without statistically significant difference. 10 pts died before evaluation of response, all of them as a consequence of bone marrow aplasia, with no difference between tt arms.
Median neutrophil-recovery time was different between tt [27days (10-74d) in 7+3 vs 31days (10-65d) in 10+3+E; p=0.02]. Median myelosuppression-recovery time (Hb>8g/dL; Leuk>1.5x109/L; Plaq>20x109/L) wasn’t statistically significant between tt (median 28days in 7+3 vs 30days in 10+3+E; p=0.216). Also the number of febrile neutropenia wasn’t different, with a median 2 episodes/patient. 16 pts required ICU admission, with no difference between tt.
Early relapse rate (≤6 months after induction tt) was 6.4%, lower in 10+3+E arm (3.6% vs 11.5%; p=0.047), regardless ELN risk. Overall relapse rate was 47% with statistically difference according to ELN risk (61% vs 50% vs 38% in unfavourable, intermediate and favourable risk; p<0.001) but no difference by tt arm (p=0.296). Median overall survival (OS) was 20months (95%CI 16-24months), without difference by tt (p=0.651).
At univariate analysis, several factors were associated with poor OS: ELN risk (p<0.001; HR 2.166), myelosuppression ≥50days (p=0.005; HR 18.717), neutropenia ≥60days (p<0.001; HR 17.711), ICU admission (p<0.001; HR 3.152) and disease relapse (p<0.001; HR 1.029). CR after induction was a protective factor (p<0.001; HR 0.389). At multivariate analysis factors that remained significant were: ELN risk (p<0.033; HR 2.148), myelosuppression ≥50days (p=0.003; HR 5.302), ICU admission (p=0.015; HR 2.706) and disease relapse (p<0.001; HR 13.937).
Conclusion
Outcomes were similar, with both induction regimens increased CR rates without increasing mortality in patients with AML fit for intensive treatment.
The only identified difference was that addiction of etoposide to 7+3 regimen had a lower early relapse rate but with slightly increased haematological toxicity. No difference was observed in overall relapse rate.
Thus, both induction regimens are effective and tolerated in fit adult patients with AML.
Keyword(s): Acute myeloid leukemia, Induction chemotherapy