Among pts with SF3B1 MT, we observed a trend for higher response in pts with the hotspot K700E, 62.7% (37/59) vs 47.4% (27/57) in non-K700E, p=.097. In pts with SF3B1 MT, divided by median VAF, we observed a trend for better HI with VAF was >38, 63.5% (33/52) vs 45.3% (24/53), p=.062...Our RWD in the largest luspa treated cohort demonstrates OS benefit to luspa response...Low baseline RBC-TB dependency, lower risk IPSS-M, SF3B1 MT, SF3B1-K700E mutation and SF3B1α co-mutations correlated with higher response rates.