BTK inhibitors acceptable treatment option for patients with CLL, severe renal impairment
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Key takeaways:
- BTK inhibitors are a therapeutic option for patients with CLL and severe renal impairment.
- Dose modifications of BTK inhibitor may help improve tolerability.
Real-world data showed that Bruton tyrosine kinase inhibitors were a reasonable therapeutic option for patients with chronic lymphocytic leukemia and severe renal impairment, including for older adults and those on dialysis.
Dose modifications of the BTK inhibitor may help improve tolerability without reducing efficacy, according to the abstract presented at ASH Annual Meeting and Exposition.
Although the most prescribed BTK inhibitor, ibrutinib (Imbruvica; Janssen, Pharmacyclics), seems safe for mild to moderate renal dysfunction, severe renal failure has been excluded from prospective studies and no guidance exists on dosing under the FDA label, according to Clare E. Anderson, MD, from Durham VA Medical Center and Duke University School of Medicine, and colleagues.
Therefore, the researchers conducted a real-world data analysis to determine the safety and tolerability of BTK inhibitors in severe renal impairment. They performed an electronic query of the VA Corporate Data Warehouse and retrospective chart review to find patients with CLL treated with a BTK inhibitor between 2013 and 2022 and who had severe chronic kidney disease overlapping with their treatment period.
In total, 115 patients received 124 lines of BTK inhibitors, according to the abstract. The median duration of follow-up from the start of therapy was 26 months, the median patient age was 74 years and 98% of patients were men. Overall, 64% of patients had an estimated glomerular filtration rate of less than 30 at the start of therapy, with 18% requiring dialysis and the remaining 36% experiencing progressive renal dysfunction during treatment.
Anderson and colleagues reported that 103 patients were prescribed ibrutinib, 18 acalabrutinib (Calquence, AstraZeneca) and three zanubrutinib (Brukinsa, BeiGene). Most BTK inhibitors (76%) were initiated at the labeled dose. Of these, 37% later required dose reduction, mainly because of cytopenia, failure to thrive, bleeding or worsening renal function. Discontinuation of therapy for toxicity occurred in 50% of ibrutinib recipients, 39% of acalabrutinib recipients and 33% of zanubrutinib recipients, mainly due to infection, bleeding, arrhythmia and disease progression.
The median PFS was 45 months and OS was 49 months among the 103 patients who received ibrutinib.
Analysis showed that baseline severity of renal failure (HR 1.85; 95% CI, 1.21–2.88), cirrhosis (HR 6.36; 95% CI, 1.45–19.76) and heart failure (HR 4.2; 95% CI, 1.82–9.47) were all linked to shorter PFS. The results also showed that younger age, dialysis and absence of atrial fibrillation at the beginning of therapy were protective in univariate models, while heart failure and cirrhosis retained their prognostic impact on OS in multivariate models.
The investigators also found that ibrutinib dose reductions at initiation or during treatment were linked to a longer duration of therapy (median duration of treatment with ibrutinib was 33 months) and that dose reductions did not significantly decrease the response rate to ibrutinib or worsen survival.
Although kidney function did not improve after BTK inhibitor treatment in any of the 115 patients, 11 patients had CLL-related kidney dysfunction, according to the abstract. In total, 51 patients on ibrutinib and eight patients on acalabrutinib had renal impairment progression.
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