Refitting fitness in CLL

In this issue ofBlood, Al-Sawaf et al 1 report no significant outcome differences for unfit vs fit patients with chronic lymphocytic leukemia (CLL) without TP53 aberrations treated front line with standard fixed duration venetoclax plus obinutuzumab (ven-obi) in the randomized CLL14 and CLL13 trials.Fitness was a key trial inclusion determinant considering their respective chemoimmunotherapy (CIT) comparators; the CLL14 study focusing on older, unfit patients ("slow go") and randomizing to ven-obi or chlorambucil-obi, and the CLL13 study examining younger, fit patients ("go go") and randomizing to ven-regimens or fludarabine-cyclophosphamiderituximab or bendamustine-rituximab.At the time these trials started enrolling (2015-2016), the paradigm shift away from an age-centric selection of frontline CLL treatment had begun, and exploratory analyses from the CLL11 trial identified creatinine clearance (<70 mL/min) and the cumulative illness rating scale (CIRS > 6) score to reflect unfit. 1 These fitness definitions were subsequently incorporated into pivotal trials.