Using BCR-Targeted Agents for Relapsed/Refractory CLL

Before the era of novel inhibitors, individuals without 17p-deleted CLL who had a reasonable duration of response to chemo-immunotherapy were often treated with additional chemo-immunotherapy, states Jennifer Brown, MD, PhD. Today, nearly all patients with relapsed CLL, with or without the 17p deletion, will be treated with ibrutinib (Imbruvica), the novel B-cell receptor (BCR)-targeted agent unless there is a contraindication, such as in patients requiring anticoagulation or those that have bleeding diathesis or cardiac disease. In these settings, individuals may receive an alternative BCR inhibitor, such as idelalisib (Zydelig).

Many patients with CLL will receive at least one chemo-immunotherapy regimen, such as fludarabine, cyclophosphamide, and rituximab (Rituxan); bendamustine and rituximab; or rituximab and chlorambucil. The incorporation of BCR inhibitors has mainly been in the setting of relapsed or refractory CLL, says Javier Pinilla-Ibarz, MD, PhD. Targeted therapies, such as ibrutinib and idelalisib, are appropriate choices in the relapsed or refractory setting, since trials of these agents have shown to extend survival. The toxicity profile of one or the other agent may be more suitable for certain patients, he adds.

A regimen of bendamustine and rituximab that incorporates dose-reduced bendamustine (50 to 70 mg/m²) may be a reasonable strategy in situations where the patient does not tolerate BCR inhibitors, says Pinilla-Ibarz. Alemtuzumab, a CD52-directed monoclonal antibody, is a potent agent against fludarabine-refractory or 17p deleted CLL. However, despite having activity in blood- and bone marrow-based disease, it lacks significant activity in nodal disease, comments Brown.