The drug combination was unable to cure four patients, who had all visited Africa, in early signs the parasite is evolving resistance.
A team at the London School of Hygiene and Tropical Medicine said it was too early to panic.
But it warned things could suddenly get worse and demanded an urgent appraisal of drug-resistance levels in Africa.
Malaria parasites are spread by bites from infected mosquitoes.
It is a major killer of the under-fives with one child dying from the disease every two minutes.
