The teenagers, who have not been named, were arrested at two separate addresses in east London at about 22:50 BST last night.
All four have been taken to police stations in east London and are being questioned over the fatal stabbing of Adam, the nephew of Olympic sprinter John Regis.
Adam died on March 17th after being stabbed following an evening at the Showcase cinema in Beckton, east London.
Police believe he got off a bus with two friends shortly before he was attacked.
The two friends left him at some point on their journey from the bus stop and Adam was stabbed on the junction of Boundary Road and Kingsland Road in Plaistow, near West Ham United's football ground.
Adam was taken to Newham General hospital but died from his injuries later that night.
A post-mortem concluded he died from a single stab wound to the chest and abdomen.
As part of the investigation detectives made eight arrests prior to yesterday's developments.
A 17-year-old arrested on March 20th has been bailed to return to an east London police station next month, while four other males - two aged 20, an 18-year-old and a 19-year-old – were bailed after being arrested the next day.
Three other men, aged 19, 21 and 22, were also arrested but released without charge.
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