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Real-World Clinical Outcomes Among Patients With CLL, With and Without Deletion 17p, Treated With First-Line Ibrutinib
Evidence is limited for the effectiveness of ibrutinib when given as first-line monotherapy to patients with chronic lymphocytic leukemia (CLL) with deletion 17p (del[17p]), which predicts a poor response to chemoimmunotherapy and confers a negative prognosis. To fill this evidence gap, researchers conducted a retrospective analysis that compared real-world clinical outcomes of ibrutinib monotherapy in patients with CLL with or without this deletion (Haematologica. 2022; doi:10.3324/haematol.2021.280376).
“Overall, the prognosis for patients with CLL…has improved with the advent of Bruton’s tyrosine kinase (BTK) inhibitors,” wrote Anthony Mato, MD, MSCE, Memorial Sloan Kettering Cancer Center, New York, NY, and colleagues, adding, “The first drug in this class, ibrutinib, was approved by the US Food and Drug Administration (FDA) in February 2014 for the treatment of patients with relapsed/refractory (R/R) CLL.”
“This approval was based on results from the pivotal RESONATE trial, which showed that ibrutinib had efficacy in a heavily pretreated patient cohort. Following this, the RESONATE-2 trial was performed in the front-line setting and showed that ibrutinib was effective for treatment-naïve patients,” authors wrote, adding, “Based on these data, FDA approval for ibrutinib was extended to first-line (1L) therapy.”
To conduct their study, Dr. Mato and team used data from the Flatiron Health electronic health records-derived database to identify adult patients diagnosed with CLL or small lymphocytic leukemia (SLL) between 2011 and 2019 who had received cytogenetic testing and 1L ibrutinib monotherapy. They included 1,069 such patients in their analysis. Most study patients were male (63%), the mean age of the group was 69 years, and 24% had del(17p).
Results of data analysis indicated that median overall survival (OS) was shorter in patients with del(17p) than in patients without this deletion (57.7 mo vs. median not reached, P=0.0006), and results were similar for median time to next treatment (TTNT; 49.4 mo vs. median not reached, P=0.03).
Using an adjusted Cox proportional hazards model, Dr. Mato and team also found that patients with del(17p) had a 70% higher risk of death than patients without this deletion (hazard ratio, 1.7, P=0.003).
Median time to treatment discontinuation was shorter in patients with del(17p) than in patients without this deletion (32.5 mo vs. 42.9 mo, P=0.34). Moreover, rates of discontinuing ibrutinib treatment or switching to a new treatment were higher in patients with del(17p) than in patients without this deletion, although not statistically significantly so.
The most common reason for discontinuing ibrutinib therapy in both groups was toxicity. However discontinuation because of disease progression was higher in patients with del(17p) than in patients without this deletion (20% vs. 6%, P<0.0001).
“As expected, our study showed that patients with del(17p) had poorer outcomes than those without del(17p)…. Furthermore, while OS and TTNT were not reached among patients without del(17p), among patients with the deletion, mean survival following discontinuation of ibrutinib was relatively short (approximately 8 months) inferred from a median TTNT in this group [of] 49.4 months while OS was 57.7 months.”
“This study identifies an unmet need for more effective 1L therapeutic options in patients with CLL/SLL and del(17p), despite the advent of ibrutinib,” Dr Mato and team concluded.
