Case Presentation – Frontline Treatment of Older Patient with CLL: Options and Consideration

The advent of novel targeted therapies, specifically Bruton’s tyrosine kinase (BTK) inhibitors and the B-cell lymphoma 2 (BCL2) inhibitor, venetoclax, has revolutionized the treatment approach in the frontline setting for patients with chronic lymphocytic leukemia (CLL). By targeting BTK, a critical kinase in proximal B-cell receptor (BCR) signaling, this class of small molecule inhibitors impairs BCR-signaling and activation of NF-κB, and inhibits cell proliferation and migration.1,2 BCL2 is an antiapoptotic protein that is overexpressed in various B-cell cancers, including CLL.3 Venetoclax disrupts antiapoptotic signaling through BCL2, thereby inducing programmed cell death of CLL cells.4 Both of these options have significantly improved the efficacy of treatment in older patients in which efficacy of more traditional chemoimmunotherapy regimens was often hampered by increased toxicity limiting therapy. When embarking on initial therapy for patients with CLL and deciding between various options, it has become important to consider age, comorbidities, and functional condition as well as their disease specific features such as the results of their FISH and IGHV mutational status. Armed with this information, a provider can then review potential options of therapy with each patient focusing on both their disease specific features and comorbidities while taking into consideration their desire for continuous treatment versus time-limited therapy.