Do Dose Interruptions Affect Survival in Ibrutinib-Treated Patients With CLL?
Posted: Tuesday, May 5, 2020
According to a retrospective study published in Cancer Medicine, patients with chronic lymphocytic leukemia (CLL) who experience interruptions in dosing of the Bruton’s tyrosine kinase inhibitor ibrutinib experience a detriment in overall survival. Sameer A. Parikh, MD, of the Mayo Clinic, Minnesota, and colleagues, suggest that patients who continue ibrutinib treatment without interruptions appear to have better outcomes.
“Our results also confirm observations from other ‘real world’ analyses that more patients stop ibrutinib due to toxicity than due to progression of disease,” the authors concluded. “This latter finding has major implications for clinical trial design, where combination therapies with fixed duration of treatment that achieve deep remission may be more desirable than chronic long-term treatment.”
Using the Mayo Clinic database of patients with CLL, the authors focused on 299 patients who had received ibrutinib therapy. Dose modifications and temporary interruptions in therapy were recorded and then compared with outcomes. The authors analyzed event-free survival and overall survival. Of the 299 patients, 162 had relapsed or refractory disease, and 47 had progressive, treatment-naive disease. A total of 122 patients were treated with a standard starting dose of ibrutinib (420 mg daily), whereas the other 87 patients started treatment at oral doses of 280 mg or 140 mg, or 140 mg every other day.
The median follow-up was 24 months. Multivariable analyses (adjusting for age, sex, and other factors) revealed that both temporary interruption of ibrutinib therapy (hazard ratio [HR] = 2.37; P = .006) and TP53 disruption at initiation of ibrutinib therapy (HR = 1.81; P = .048) were linked to shorter event-free survival; however, TP53 disruption alone (HR = 2.38; P = .015) was associated with shorter overall survival. Neither the starting dose nor the dose modifications impacted these survival outcomes.
Disclosure: The study authors’ disclosure information can be found at onlinelibrary.wiley.com.