Chronic lymphocytic leukaemia – emerging treatment options: a report from the ASH Meeting 2009
Chronic lymphocytic leukaemia (CLL) in early stages does not require immediate treatment. Although some patients progress rapidly, institution of treatment in an asymptomatic phase has so far not been demonstrated to be beneficial and is best deferred to the time of disease progression. Some early stage patients do not progress for a prolonged period of time and may indeed never need treatment. For patients requiring treatment, risk-adapted strategies have been defined in recent trials. Importantly, age itself should not be used to preclude patients from more intensive protocols, with performance status and presence or absence of co-morbidities being the recommended criteria for treatment adjustments. Whilst fitter patients without significant co-morbidity are initially best treated with immunochemotherapy protocols, aiming at achieving maximum tumour reduction and a status of negativity for minimal residual disease (MRD), less intensive strategies seem to be preferable for the less fit, "slow-go" patient. The CLL8 study has now set the current standard for first-line treatment of the "go-go" patient, showing that rituximab + fludarabine and cyclophosphamide (R–FC) improve not only response rates and progression-free survival as compared to fludarabine and cyclophosphamide (FC), but also overall survival. Currently, studies are ongoing trying to further improve over this standard. For patients with co-morbidity, chlorambucil might still be a valuable treatment option. Initial results of ongoing studies seem to indicate that outcome might be further improved by combination of this drug with rituximab. Combination protocols and lenalidomide are currently investigated for their therapeutic efficacy in "go-go" as well as "slow-go" patients. Cytogenetic and biological characteristics of the disease are also getting increasingly important for treatment selection. Currently, CLL cases with 17p deletion are defined as separate subgroup, with poor response to fludarabine- and alkylator-based chemotherapy protocols and also only poor results achievable by R–FC. For this high-risk patient group, alemtuzumab including combination treatments are recommended and for selected patients, several groups are testing a strategy using allogeneic transplantation with full or reduced intensity conditioning.