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Four fire engines and around 25 firefighters were called to a flat fire on Goldcrest Close in Thamesmead.
Firefighters wearing breathing apparatus brought one man out of the affected flat. Sadly the man was pronounced dead at the scene.
Fire crews led one man and two women from neighbouring flats. They were all uninjured.
The Brigade was called at 0604 and the fire was under control by 0740. Firefighters from Plumstead, Erith and Bexley fire stations attended the scene. The cause of the fire is under investigation.