STANDARD-RISK RANDOMIZATION OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA IN TRIAL AIEOP-BFM ALL 2000 INDICATES EQUAL OUTCOME WITH REDUCED-INTENSITY DELAYED INTENSIFICATION IN ETV6-RUNX1-POSITIVE PATIENTS
(Abstract release date: 05/18/17)
EHA Library. Bleckmann K. 06/24/17; 181767; S480
Kirsten Bleckmann
Contributions
Contributions
Abstract
Abstract: S480
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 17:00 - 17:15
Location: Hall E
Background
ETV6-RUNX1 fusion is a common genetic aberration in childhood acute lymphoblastic leukemia (ALL) and is associated with good prognosis in the context of contemporary treatment regimens. The required treatment intensity for this well-described biologic subgroup with low risk of relapse is not known so far. In trial AIEOP-BFM ALL 2000, feasibility of reduction of delayed intensification treatment to reduce the burden of chemotherapy was tested in a randomized approach in the standard-risk group. Treatment reduction was not successful in the total cohort (8-year probability of disease-free survival (8y-pDFS, ± standard error) 89.2 ± 1.3% for reduced delayed intensification treatment, 92.3 ± 1.2% for the standard treatment (log-rank P = 0.04)) due to evidence of more relapses observed in patients treated less intensively.
Aims
The retrospective subgroup analysis presented here focuses on the ETV6-RUNX1-positive patients included in the group of randomized standard-risk patients.
Methods
From 07/2000 to 06/2006, 4741 eligible patients with ALL (age range 1-17 years) were enrolled in the trial AIEOP-BFM ALL 2000 (NCT 00430118 (BFM) and NCT 00613457 (AIEOP)). Of those, 1164 patients were considered at standard risk of relapse, defined by lack of genetic high-risk criteria and absence of minimal residual disease at day 33 and week 12 of treatment (tested by immunoglobulin/T-cell receptor gene rearrangement polymerase chain reaction). They were randomly assigned to either receive the reduced-intensity protocol III (P-III), or standard protocol II (P-II) for delayed intensification. P-III is shorter than P-II (duration 29 vs 49 days), the dose of dexamethasone in P-III is 30% lower, and the dose of vincristine, doxorubicin, and cyclophosphamide are reduced by 50% as compared to P-II. The intention was to prove non-inferiority of the reduced-intensity treatment compared to standard treatment.
Results
ETV6-RUNX1-positive patients (n = 367) accounted for 34% of randomized standard-risk patients (Age: < 6 years n = 260, 6 to <10 years n = 79, ≥ 10 years n = 28; early cytologic response evaluation in bone marrow on day 15 of induction treatment: M1 n = 218, M2 n = 74). Of those, 188 were treated with the experimental P‑III, 179 received the standard P-II. With a median follow-up of 8.6 years, the as-treated analysis showed an 8y-pDFS of 94.5 ± 1.7% for P-III, and 94.4 ± 1.8% for patients with P-II (log-rank P = 0.74). Cumulative incidence of relapse at 8 years was 3.3 ± 1.3% and 4.3 ± 1.6% (Gray P = 0.09), and 8-year overall survival was 96.9 ± 1.4% and 98.8 ± 0.9% (P = 0.27) for P‑III and P‑II, respectively. Analysis of ETV6-RUNX1-positive patients by age groups or treatment response on day 15 allowed no further refinement of prognostic subgroups.
Conclusion
There was no evidence of prognostic disadvantage in ETV6-RUNX1-positive standard-risk patients when treated with the reduced-intensity experimental arm. No clear age- or response-dependent differences could be revealed for this group, which is in line with the biologic understanding of this genetic subgroup.
Hence, it might be postulated that treatment reduction might be feasible in this clearly defined biologic subgroup. However, the present data is not result of a sufficiently powered non-inferiority study question focused on the subgroup of ETV6-RUNX1-positive patients, but reflects a subgroup analysis with descriptive character. Therefore, any decision for treatment reduction should be considered carefully.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): TEL-AML1, Randomized, Pediatric, Acute lymphoblastic leukemia
Abstract: S480
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 17:00 - 17:15
Location: Hall E
Background
ETV6-RUNX1 fusion is a common genetic aberration in childhood acute lymphoblastic leukemia (ALL) and is associated with good prognosis in the context of contemporary treatment regimens. The required treatment intensity for this well-described biologic subgroup with low risk of relapse is not known so far. In trial AIEOP-BFM ALL 2000, feasibility of reduction of delayed intensification treatment to reduce the burden of chemotherapy was tested in a randomized approach in the standard-risk group. Treatment reduction was not successful in the total cohort (8-year probability of disease-free survival (8y-pDFS, ± standard error) 89.2 ± 1.3% for reduced delayed intensification treatment, 92.3 ± 1.2% for the standard treatment (log-rank P = 0.04)) due to evidence of more relapses observed in patients treated less intensively.
Aims
The retrospective subgroup analysis presented here focuses on the ETV6-RUNX1-positive patients included in the group of randomized standard-risk patients.
Methods
From 07/2000 to 06/2006, 4741 eligible patients with ALL (age range 1-17 years) were enrolled in the trial AIEOP-BFM ALL 2000 (NCT 00430118 (BFM) and NCT 00613457 (AIEOP)). Of those, 1164 patients were considered at standard risk of relapse, defined by lack of genetic high-risk criteria and absence of minimal residual disease at day 33 and week 12 of treatment (tested by immunoglobulin/T-cell receptor gene rearrangement polymerase chain reaction). They were randomly assigned to either receive the reduced-intensity protocol III (P-III), or standard protocol II (P-II) for delayed intensification. P-III is shorter than P-II (duration 29 vs 49 days), the dose of dexamethasone in P-III is 30% lower, and the dose of vincristine, doxorubicin, and cyclophosphamide are reduced by 50% as compared to P-II. The intention was to prove non-inferiority of the reduced-intensity treatment compared to standard treatment.
Results
ETV6-RUNX1-positive patients (n = 367) accounted for 34% of randomized standard-risk patients (Age: < 6 years n = 260, 6 to <10 years n = 79, ≥ 10 years n = 28; early cytologic response evaluation in bone marrow on day 15 of induction treatment: M1 n = 218, M2 n = 74). Of those, 188 were treated with the experimental P‑III, 179 received the standard P-II. With a median follow-up of 8.6 years, the as-treated analysis showed an 8y-pDFS of 94.5 ± 1.7% for P-III, and 94.4 ± 1.8% for patients with P-II (log-rank P = 0.74). Cumulative incidence of relapse at 8 years was 3.3 ± 1.3% and 4.3 ± 1.6% (Gray P = 0.09), and 8-year overall survival was 96.9 ± 1.4% and 98.8 ± 0.9% (P = 0.27) for P‑III and P‑II, respectively. Analysis of ETV6-RUNX1-positive patients by age groups or treatment response on day 15 allowed no further refinement of prognostic subgroups.
Conclusion
There was no evidence of prognostic disadvantage in ETV6-RUNX1-positive standard-risk patients when treated with the reduced-intensity experimental arm. No clear age- or response-dependent differences could be revealed for this group, which is in line with the biologic understanding of this genetic subgroup.
Hence, it might be postulated that treatment reduction might be feasible in this clearly defined biologic subgroup. However, the present data is not result of a sufficiently powered non-inferiority study question focused on the subgroup of ETV6-RUNX1-positive patients, but reflects a subgroup analysis with descriptive character. Therefore, any decision for treatment reduction should be considered carefully.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): TEL-AML1, Randomized, Pediatric, Acute lymphoblastic leukemia
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