Minimal residual disease in chronic lymphocytic leukaemia: is it ready for primetime?

Abstract

New therapeutic modalities have substantially improved response rates and outcomes in chronic lymphocytic leukaemia (CLL), yet the mindset remains that palliation is the only goal of therapy because the disease is considered incurable. Ultimately, all patients relapse despite achieving an initial response, as minimal residual disease (MRD) persisting after therapy eventually evolves into morphological and clinical recurrence. The emergence of immune-based combination therapies capable of inducing molecular remissions, the availability of highly sensitive assays that detect MRD, and emerging data showing a longer duration of response or longer survival in patients with no detectable disease, suggest that eradicating MRD may be a reasonable option for some patients. Moreover, novel biological prognostic markers have divided CLL into favourable and unfavourable subtypes, arguing in favour of defining different goals of therapy for different patients. Clinicians are increasingly challenged with the task of how best to incorporate MRD assessment into clinical practice, especially in an era when these novel prognostic factors exist. This review summarises the current understanding of MRD from a clinical standpoint, suggests that MRD eradication maybe a reasonable option for some patients, and argues in favour of designing large randomised studies to determine whether MRD-negative remission improves outcome.