Cause-Specific Mortality and Prognostic Impact of Comorbidity in Japanese Patients With Chronic Lymphocytic Leukemia

Abstract

Background: Due to its rarity, there are very limited data available on the cause of death (COD) and its association with comorbidities in Japanese chronic lymphocytic leukemia (CLL) patients.

Methods: To investigate the prevalence of comorbidities and their impact on cause-specific mortality, we retrospectively reviewed 121 Japanese patients with CLL.

Results: The median age was 69 years, with 47.9% having at least one comorbidity listed in the Charlson Comorbidity Index (CCI), and 12.4% were multimorbid. With a median follow-up of 74 months, the 5- and 10-year overall survival rates were 80.6% and 60.1%, respectively. Among the 44 deaths observed, CLL progression was the leading COD (38.6%), which together with infections and other malignancies accounted for nearly 80%. Patients with higher CCI risk categories had significantly higher 5-year all-cause mortality (CCI 1-2: 22.9% and ≥ 3: 31.4%) and non-CLL-specific mortality (CCI 1-2: 18.8% and ≥ 3: 31.4%) compared to those without (CCI 0: 12.6%, p = 0.005; 3.5%, p < 0.001, respectively), whereas CLL-specific mortality was not influenced. On multivariate analysis, age and CCI retained a significant prognostic impact on all-cause mortality (hazard ratio [HR] 1.08, p < 0.001 and HR 1.88, p = 0.004, respectively) and non-CLL-specific mortality (HR 1.12, p < 0.001 and HR 3.81, p < 0.001, respectively).

Conclusions: Our study showed that CLL itself was the leading COD, and comorbidity burden was associated with non-CLL-specific deaths. This highlights the importance of better disease control and effective management of comorbidities.

Keywords: CCI; CLL; cause of death and BTKi; comorbidities.

FIGURE 1

Bar chart illustrating the distribution of cause of death in this Japanese CLL cohort. (A) COD in all patients, (B) COD in patients diagnosed before 2010, and (C) since 2010. CLL, chronic lymphocytic leukemia; COD, cause of death.

FIGURE 2

Swimmer plot demonstrating the clinical course of patients according to whether the cause of death was CLL progression. BTKi, Bruton's tyrosine kinase inhibitor; CLL, chronic lymphocytic leukemia.

FIGURE 3

Cumulative incidence and details of infectious disease hospitalization. (A) Time to first infectious disease hospitalization from diagnosis. (B) Detailed reasons for hospitalization. CI, cumulative incidence; COVID‐19, coronavirus disease 2019; VZV, varicella‐zoster virus.

FIGURE 4

Five‐year cause‐specific mortality according to the CCI risk categories. (A) All‐cause mortality, (B) non‐CLL‐specific cause mortality, (C) CLL‐specific mortality. CCI, Charlson Comorbidity Index; CI, cumulative incidence; CLL, chronic lymphocytic leukemia.