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Hi Andrew, I too hope the phase III pelabresib trial is a smashing success. But the discussion above--and please correct me if I am wrong--appears to compare findings from the phase III ruxolitinib study, published in NEJM 2012, with the more recent phase II study of ruxolitinib plus pelabresib study published in the JCO in 2023. If so, please note that the landmark ruxolitinib registration trial patients were quite ill. 68% were pretreated with a leukemogenic chemotherapy (hydoxyurea), a regimen now rarely given first line (presumably few to none of the pelabresib combo cohort received this). 58% or the ruxolitinib patients had IPPS high risk disease, versus 16% in the phase II pelabresib combo cohort. None of the phase III single agent ruxolitinib patients had low risk disease, versus 24% of the patients in the combo phase II trial. Some of the phase III ruxolitinib patients were ECOG category 3--unable to work outside the home and capable of only limited self-care. None of the phase II combo patients were this ill. So yes, 68% of the patients in the combo arm versus 42% in the ruxolitinib arm had a 35% or better reduction in spleen size...but the patients were healthier to begin with, and potentially more likely to have a beneficial response. Or is there a better comparator trial I am overlooking?

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