Abstract
Chronic lymphocytic leukemia is a disease of older patients, most of them suffering from significant comorbidities or functional limitations (so-called 'slow-go' patients). Unfortunately, clinical trials in chronic lymphocytic leukemia have until recently focused mainly on the subgroup of younger patients in good overall condition ('go-go' patients).
Clinico-biological parameters, such as performance status, calculated creatinine clearance, the number and severity of comorbidities along with individual clinical assessment can help guide decisions relating to the objectives and ultimately the intensity of treatment. Two large randomized studies have recently demonstrated that the addition of monoclonal antibodies against CD20 (obinutuzumab, rituximab and ofatumumab) to chlorambucil in untreated 'slow- go' patients resulted in a significant increase in the number of complete remissions, progression-free survival and even overall survival (for obinutuzumab and rituximab) with an acceptable safety profile.
Chemoimmunotherapy combining chlorambucil with anti-CD20 antibody is thus the new standard 1st line therapy in this group of patients. Treatment of relapsed/ refractory chronic lymphocytic leukemia in 'slow-go' patients is very difficult and specific data is sparse.
In this indication, we have witnessed an extraordinary breakthrough by means of small oral inhibitors interfering with B-cell receptor downstream signaling pathways: ibrutinib, the Bruton's tyrosine kinase inhibitor, and idelalisib, the inhibitor of phosphatidylinositol 3-kinase δ. Both drugs radically changed the approach to the treatment of relapsed/ refractory chronic lymphocytic leukemia; relatively mild toxicity also predetermines their use in elderly/ comorbid patients.
Other treatment options for relapsed/ refractory chronic lymphocytic leukemia in this subgroup include alemtuzumab, ofatumumab, high-dose glucocorticoids + antiCD20 antibodies, or bendamustine + rituximab regimen.