AALL1331
AALL1331 tested swapping blocks of harsh chemotherapy for the antibody blinatumomab in children whose leukaemia had come back; the antibody caused far fewer serious infections, more patients survived in the higher-risk group, and children whose relapse was in the bone marrow did better in the low-risk group too.
Overview
AALL1331 was a Children's Oncology Group phase 3 trial at 155 hospitals in the United States, Canada, Australia and New Zealand. All 669 patients received a four-week reinduction block and were then stratified. High- and intermediate-risk patients were randomised to two cycles of blinatumomab or two cycles of multi-agent chemotherapy, each followed by transplant. Low-risk patients were randomised to standard chemotherapy or chemotherapy with three blinatumomab blocks in place of some chemotherapy cycles. The primary endpoint in each stratum was disease-free survival.
In the high- and intermediate-risk randomisation, closed early on the monitoring committee's advice, two-year disease-free survival was 54.4 percent with blinatumomab against 39.0 percent with chemotherapy, a difference that did not reach the trial's threshold, while two-year overall survival was 71.3 against 58.4 percent and serious infections, sepsis and mucositis were far less common with blinatumomab. In the low-risk stratum the overall difference was not significant, but the two thirds of patients whose relapse involved the bone marrow had better disease-free and overall survival with blinatumomab, and the authors describe that as a new standard for them.
- 54.4 vs 39 out of 100 alive without the cancer coming back at 2 years with Blinatumomab consolidation then transplant compared with Chemotherapy consolidation then transplant; 15.4 more per 100.
- Roughly one extra person helped for every 6 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Put another way, the treated group had about 30 percent lower chance of the event at any given time (hazard ratio 0.7, likely range 0.47 to 1.03).
- The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 61.2 vs 49.5 out of 100 alive without the cancer coming back at 4 years with Chemotherapy with blinatumomab blocks compared with Chemotherapy alone; 11.7 more per 100.
- Roughly one extra person helped for every 9 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.089) means the difference could plausibly be due to chance.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 71.3 vs 58.4 out of 100 alive at 2 years with Blinatumomab consolidation then transplant compared with Chemotherapy consolidation then transplant; 12.9 more per 100.
- Roughly one extra person helped for every 8 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Put another way, the treated group had about 38 percent lower chance of the event at any given time (hazard ratio 0.62, likely range 0.39 to 0.98).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 15 vs 65 out of 100 reached this endpoint with Blinatumomab consolidation then transplant compared with Chemotherapy consolidation then transplant; 50 fewer per 100.
- Roughly one extra person helped for every 2 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- 90.4 vs 79.6 out of 100 alive at 4 years with Chemotherapy with blinatumomab blocks compared with Chemotherapy alone; 10.8 more per 100.
- Roughly one extra person helped for every 9 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.11) means the difference could plausibly be due to chance.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 72.7 vs 53.7 out of 100 alive without the cancer coming back at 4 years with Chemotherapy with blinatumomab blocks compared with Chemotherapy alone; 19 more per 100.
- Roughly one extra person helped for every 5 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.015) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Children, adolescents and young adults aged 1 to 30 with a first relapse of B-cell acute lymphoblastic leukaemia: after one block of reinduction chemotherapy, blinatumomab in place of intensive consolidation chemotherapy (high and intermediate risk, then transplant) or intercalated with chemotherapy (low risk). People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
669 enrolled.
174 patients with marrow relapse across both arms
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Disease-free survival at 2 years, high- and intermediate-risk relapseprimary | Blinatumomab consolidation then transplant | 105 | 54.4% | 0.7 (0.47 to 1.03) | 0.03 (one-sided) | link |
| Chemotherapy consolidation then transplant | 103 | 39% | ||||
| Overall survival at 2 years, high- and intermediate-risk relapse | Blinatumomab consolidation then transplant | 105 | 71.3% | 0.62 (0.39 to 0.98) | 0.02 (one-sided) | link |
| Chemotherapy consolidation then transplant | 103 | 58.4% | ||||
| Serious infection as an adverse event, high- and intermediate-risk relapse | Blinatumomab consolidation then transplant | - | 15% | - | - | link |
| Chemotherapy consolidation then transplant | - | 65% | ||||
| Disease-free survival at 4 years, low-risk relapseprimary | Chemotherapy with blinatumomab blocks | - | 61.2% | - | 0.089 | link |
| Chemotherapy alone | - | 49.5% | ||||
| Overall survival at 4 years, low-risk relapse | Chemotherapy with blinatumomab blocks | - | 90.4% | - | 0.11 | link |
| Chemotherapy alone | - | 79.6% | ||||
| Disease-free survival at 4 years, low-risk relapse involving the bone marrow | Chemotherapy with blinatumomab blocks | - | 72.7% | - | 0.015 | link |
| Chemotherapy alone | - | 53.7% |
Blinatumomab belongs in the treatment of low-risk marrow relapse in children; isolated extramedullary relapse needs new approaches.
Blinatumomab consolidation is a safer bridge to transplant for children with higher-risk relapsed B-ALL and improved survival; it is the basis for using blinatumomab in place of chemotherapy blocks after relapse.
Similar pages
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