Sequential and combination treatments with novel agents in chronic lymphocytic leukemia

Abstract

Chemoimmunotherapy has been the standard of care for patients with chronic lymphocytic leukemia for a long time. However, over the last few years, novel agents have produced unprecedented outcomes in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia. With the advent of these targeted agents, treatment options have diversified very considerably and new questions have emerged. For example, it is unclear whether these novel agents should be used as sequential monotherapies until disease progression or whether they should preferably be combined in time-limited treatment regimens aimed at achieving deep and durable remissions. While both approaches yield high response rates and long progression-free and overall survival, it remains challenging to identify patients individually for the optimal concept. This review provides guidance in this decision process by presenting evidence on sequential and combined use of novel agents and discussing the advantages and drawbacks of these two approaches.

Figure 1.

Targets of currently approved (black) and investigated (gray) novel agents. CLL: chronic lymphocytic leukemia; BCR: B-cell receptor. This figure was produced by M. Fürstenau using servier medical art (smart.servier.com).

Figure 2.

Proposed algorithm for first-line treatment using approved options in clinical practice. y: years; R: rituximab; FCR: fluradabine, cyclophosphamide, rituximab; BR: bendamustine, rituximab; Clb-G: chlorambucil, obinutuzumab.

Figure 3.

Proposed sequencing of therapy according to first-line treatment; approved options. CT: chemotherapy; CIT: chemoimmunotherapy; y: years; M: mutated; UM: unmutated; R: rituximab; BTKi: Bruton tyrosine kinase inhibitor.