Chemo‐immunotherapy for Older Patients with Chronic Lymphocytic Leukemia – Time to Retire?

In this issue of HemaSphere, Danilov et al suggest, based on the Alliance for Clinical Trials in Oncology study comparing ibrutinib with or without rituximab vs bendamustine and rituximab, that a potential role for chemo-immunotherapy (CIT) still exists in the management of older patients with chronic lymphocytic leukemia (CLL). On the contrary, in our opinion, this paper further supports the central role of the BTK inhibitor (BTKi) in the elderly and finally launches a chemo-free era in CLL. Clinical trials have been designed in recent years to optimize the management of patients aged ≥65 years or unfit (the vast majority of CLL patients). Age alone is a poor prognostic factor for life expectancy and treatment tolerance. Furthermore, elderly CLL patients often present with poor performance status, comorbidities and impaired renal function, which hamper treatment with intensive regimens. Patients enrolled in Woyach et al study, though ≥65 years, should be considered a highly selected population as they were deemed suitable for bendamustine at the full dose of 90mg/m if randomized to the control arm. The patients functional status performed at baseline is representative of a healthy fit population that does not reflect those normally seen in everyday practice. Even in this selected population, like in previous clinical trials, a high percentage (25–33%) of patients ≥65 years have to discontinue bendamustine before treatment completion or to reduce the dose. Attenuated doses of the drug are frequently applied outside clinical trials although no prospective studies have been performed supporting such reduction. As a result, the PFS curves observed in trials may