Introduction: The evaluation of fitness status is a key factor in determining treatment strategies for Chronic Lymphocytic Leukemia (CLL). International guidelines, including those from ESMO and NCCN, recommend assessing fitness prior to initiating therapy, although no universally accepted definition currently exists. In many clinical trials, fitness has been assessed using the Cumulative Illness Rating Scale (CIRS) in combination with creatinine clearance.

The Comprehensive Geriatric Assessment (CGA) provides a more holistic overview, supporting both treatment selection and toxicity management. This multidimensional and interdisciplinary tool evaluates functional and cognitive abilities, comorbidities, psychological and social factors, economic status, and environmental context. However, due to its complexity and time demands, CGA is rarely implemented in routine clinical practice.

In contrast, the Geriatric-8 (G8) screening tool offers a faster and validated method to identify frailty in elderly cancer patients. It assesses nutritional status, weight loss, BMI, mobility, psychological well-being, polypharmacy, self-rated health, and age group (<80, 80–85, >85 years). The test takes approximately 3–5 minutes and provides a score ranging from 0 to 17. A score ≤14 is considered indicative of frailty and can guide treatment intensity.

Simplified tools such as the G8 may facilitate broader, standardized fitness assessment in everyday hematologic practice, ultimately enhancing personalized care.

Aim and Methods: We retrospectively calculated the G8 score in 239 consecutive CLL patients treated with targeted therapies at the Hematology Unit of Careggi Hospital, Florence, between 2016 and 2025, including both treatment-naïve and relapsed/refractory (R/R) patients.

Treatment regimens included: ibrutinib (n=111), acalabrutinib (n=29), zanubrutinib (n=16), venetoclax monotherapy (n=21), venetoclax plus rituximab (VR, n=21), venetoclax plus obinutuzumab (VO, n=21), and ibrutinib plus venetoclax (I+V, n=20).

The aim was to evaluate the feasibility of G8 assessment and its utility in predicting overall survival (OS), progression-free survival (PFS), and adverse events.

Results: The mean age at treatment initiation was 70 years (range 29–92); 120 (49%) patients were treatment-naïve, and 118 were R/R. The median number of prior treatments was 2 (range 1–6), and median follow-up was 30 months (range 0.2–132).

A G8 score ≤14 (unfit) was found in 59 patients (24.7%): 32 (26.7%) in the treatment-naïve group and 27 (22.9%) in the R/R group. Distribution by treatment type showed score ≤14 in: ibrutinib (29/111, 26.4%), acalabrutinib (12/26, 46.2%), zanubrutinib (4/16, 25%), VO (1/21, 4.8%), VR (3/21, 14.3%), venetoclax monotherapy (8/21, 40%), and I+V (2/20, 10%).

Median OS was 109.6 months for fit patients versus 40.5 months for unfit patients (p<0.001). In treatment-naïve patients, median OS was not reached at 120 months for fit patients vs 65.2 months for unfit (p<0.001); in the R/R cohort, median OS was 89.2 vs 36.6 months, respectively (p<0.001).

Median PFS was significantly longer in fit patients (55.2 vs 31.9 months, p<0.001). In the naïve cohort, median PFS was not reached in fit patients (at 120 months) vs 33.5 months in unfit (p=0.014). In the R/R group, median PFS was 50.2 vs 30.3 months in fit vs unfit patients (p=0.001).

Adverse events (any grade) were reported in 66/239 patients (27%): 22/59 (37%) in the unfit group and 44/175 (25%) in the fit group (p=0.073).

Conclusion: Defining patient fitness is essential in guiding CLL treatment strategies. The G8 score is a fast and practical tool that helps identify patients at higher risk, as it was predictive of both OS and PFS in our cohort. Interestingly, even without formal scoring, patients subjectively judged as “fit” were often treated with fixed-duration regimens, while unfit patients received continuous therapies. These results were obtained through retrospective G8 score application; prospective studies are needed to validate its utility and effectiveness in real-world clinical settings.

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2025
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