Among patients with chronic lymphocytic leukemia (CLL) undergoing treatment with ibrutinib, age does not appear to be an independent predictive factor of clinical outcomes, according to research published in Blood Advances.

CLL is diagnosed most frequently among individuals aged between 65 and 74 years of age. Age and comorbidities are known to be predictive of tolerance to treatment, and the cumulative illness rating scale (CIRS) is typically used to determine the likelihood of adverse treatment outcomes in this patient population.

Ibrutinib, an inhibitor of Bruton tyrosine kinase, since its introduction in CLL care, has proven to be superior to many treatment regimens that preceded it. Many patients, however, discontinue ibrutinib because of adverse events, though the specific characteristics that predict such discontinuation were not previously well defined.

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For this study, researchers evaluated data from patients with CLL treated with ibrutinib to determine what factors predict clinical outcomes. The evaluated outcomes included progression-free survival (PFS), event-free survival (EFS), overall survival (OS), toxicity-related discontinuation (Tox-DTD), and permanent dose reduction (PDR). All patients were treated outside of the clinical trial setting.

Overall, data from 712 patients were included. In the cohort, the average age was 70.1 years (range, 40-95), 67.1% of patients were male, 84.4% had an Eastern Cooperative Oncology Group performance status score of 0 or 1, and the mean CIRS score was 5 (range, 0-30).

Cox proportional regression hazard models showed that age (hazard ratios [HRs] for PFS, EFS, OS, Tox-DTD, and PDR, 0.82, 0.83, 0.85, 0.91, 0.73, respectively; all P >.2) was not an independent predictive factor of the evaluated outcomes. Performance status, however, predicted PFS, EFS, OS, and Tox-DTD (HRs, 2.43, 2.63, 3.90, 3.30, respectively; all P <.001), but not PDR (HR, 1.52; P =.112).

While a CIRS score of greater than 6 did not predict any of the evaluated outcomes, a single severely impaired organ by CIRS criteria predicted PDR only (HR, 1.72; P =.024). In the study, 17p deletion and TP53 mutation were predictive of PFS, EFS, and OS, but not of Tox-DTD or PDR.

“Despite the limitation related to its retrospective nature, our study showed that CIRS > 6, even with ibrutinib, remains an informative tool for predicting outcome,” the authors wrote. “Greater awareness of the vulnerability of patients with baseline neutropenia should be recommended.”

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Tedeschi A, Frustaci AM, Mauro FR, et al. Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib? Blood Adv. 2021;5(24):5490-500. doi:10.1182/bloodadvances.2021004824