Post-remission intervention with alemtuzumab or rituximab to eradicate minimal residual disease in chronic lymphocytic leukemia: where do we stand?

The introduction of purine nucleoside analogs, later in combination with alkylating moieties and anti-CD20 immunotherapy, has profoundly improved the response rate and response duration in patients with chronic lymphocytic leukemia (CLL). The quality of clinical response following treatment may be improved to a level where residual leukemic cells become undetectable. As patients with this type of response appear to have extended survival rates, minimal residual disease (MRD) eradication is considered a new objective in CLL treatment with the aim of improving progression-free survival (PFS) and potentially overall survival (OS). This review therefore aims to overview the prognostic value of MRD eradication in CLL, the role of post-remission intervention with "passive" immunotherapy (alemtuzumab or rituximab) so as to eliminate persistent MRD or prevent MRD relapse, the impact of these strategies on disease-free survival and their possible adverse consequences. The data indicate a potential for post-remission alemtuzumab or rituximab to prolong PFS in CLL, although more investigations and longer follow-up are required before MRD-guided strategies can be recommended outside of clinical trials.