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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.
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.
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.
Shares Relapsed and refractory acute lymphoblastic leukaemia in children, Blinatumomab, Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Thioguanine, Children's Oncology Group (COG), Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Children's Oncology Group (COG), Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Children's Oncology Group (COG), Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Relapsed and refractory acute lymphoblastic leukaemia in children, Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Children's Oncology Group (COG), Leukaemia (all types) and the tag soc-trials.
Shares Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.