Use of Ibrutinib in CLL: Update 5 Years After Approval
Posted: Thursday, December 5, 2019
Although ibrutinib revolutionized the treatment of chronic lymphocytic leukemia (CLL), the majority of patients who receive this Bruton’s tyrosine kinase (BTK) inhibitor still do not achieve complete remission, according to a review article published in Hematological Oncology by Stefano Molica, MD, of the Azienda Ospedaliera Pugliese‐Ciaccio, Catanzaro, Italy, and colleagues. In fact, they noted, 20% of patients develop ibrutinib-resistant cancerous clones, and about one-third of patients develop toxicities that lead to treatment discontinuation.
To answer remaining questions regarding the issues of toxicity, resistance, and remission with ibrutinib, the research team evaluated existing clinical trials of the effectiveness of this agent since its approval 5 years ago. The team focused on patients with relapsed or refractory CLL.
The investigators found that alternative treatment options may benefit patient survival, including the use of combination agents such as venetoclax. Combination therapies may be especially beneficial among those patients with high-risk disease, for whom rapid disease eradication is most advantageous; they include those with refractory disease, or those with TP53 aberrations or complex karyotypes. The investigators suggest that ibrutinib monotherapy be used as a sequential treatment approach among patients with low-risk disease, especially elderly patients with a higher burden of comorbidities. More recently, second-generation BTK inhibitors are garnering research interest as treatment options. The researchers propose that improvements in the development of chimeric antigen receptor T-cell therapy may also improve outcomes in these patients.
“Long‐term results of ongoing studies combining ibrutinib with (chemo)‐immunotherapy or other targeted agents are eagerly awaited. Future clinical trials are indeed still needed to provide answers to these open questions,” the investigators concluded.
Disclosure: The study authors reported no conflicts of interest.
