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The 34-year-old was defeated by unanimous decision, with scores of 117-110, 119-108 and 119-108.
The fight, which took by at the Madison Square Garden in New York, saw Lomachenko make a very impressive start.
The Ukrainian dropped Commey in the seventh round, leaving the Ghanaian very wobbly and rattled in the ring.
Having dominated for long, he went ahead to plead Commey’s corner to stop the fight but they didn’t oblige.
Commey, however, managed to hold his own and prevented Lomachenko from winning by a knockout.
The Ukrainian, though, proved too good and more prepared, and landed several quality body punches with his sharp shots.
In the end, the judges rightly rewarded Lomachanko for his dominant performance by scoring him a win by unanimous decision.