Adding the drug quizartinib to intensive chemotherapy did not clearly help people over 60 with acute myeloid leukaemia (AML) live longer overall, a randomised trial in the UK has found. Deaths not caused by the leukaemia coming back were more frequent with the drug. The results of the trial, called AML18, appeared in the journal Blood.
AML is a cancer of the cells in the bone marrow that make blood cells. The trial also took in people with high-risk myelodysplastic syndrome, a related disease of the bone marrow. In some people with AML, the leukaemia cells carry a change in a gene called FLT3. Quizartinib belongs to a group of medicines called tyrosine kinase inhibitors, which block signals that cells use to grow. The researchers wanted to know whether adding it helps older people live longer, whether or not their leukaemia carries the FLT3 change.
Chance decided twice
Four hundred and sixty-three people took part. Their median age was 68, meaning half were younger and half older. Chance decided who received quizartinib. Those who did took it for 14 days straight after the second and third courses of chemotherapy, plus 28 more days. They were then divided by chance a second time: one group took it as maintenance treatment for 12 further courses of 28 days each (long quizartinib), the other stopped (short quizartinib).
Three hundred and fourteen participants had no change in FLT3, and 116 had one. The median follow-up was 76 months. The trial was designed to measure overall survival, meaning how long people lived, in all participants regardless of FLT3.
No overall gain, longer survival in a planned subgroup
Across all participants, quizartinib brought no clear survival benefit: the difference seen may be due to chance. Deaths not caused by a return of the leukaemia, on the other hand, were clearly more frequent with quizartinib.
A subgroup analysis planned in advance, which looks at only part of the participants, examined the 116 people whose leukaemia carried an FLT3 change. Those among them who received quizartinib lived longer than those who did not. The hazard ratio was 0.59, which means that at any given time their risk of dying was lower than without the drug. According to the researchers, this came from a lower risk of the leukaemia coming back, and the benefit was greater with short quizartinib. In people without the FLT3 change, there was no survival benefit and no lower risk of the leukaemia coming back.
There was no clear difference in the time it took for blood counts to recover or in how long people stayed in hospital. The most frequent severe side effect in the trial was febrile neutropenia: a fever while the white blood cells that fight infection are very low.
Researchers see a benefit with the FLT3 change
The researchers conclude that adding quizartinib to intensive chemotherapy, held back until the second course, lengthened overall survival in older people whose AML carries an FLT3 change. In people who were not selected by FLT3 status, it did not improve overall survival.
