1141 - Reduced predictive value of elevated Beta-2-microglobulin plasma levels on time to first treatment in newly diagnosed CLL patients with compromised kidney function

Introduction: The clinical course of newly diagnosed CLL is extremely heterogeneous. Predictive indices, such as the CLL-IPI were developed to help identify patients who require therapy relatively soon after diagnosis. Besides dysfunctional TP53 and unmutated IGHV status, elevated beta-2-microglobulin (B2M) plasma levels were shown to most effectively filter patients at high risk for short time to first therapy (TTFT) in the weighted risk score of the CLL-IPI. However, B2M plasma levels are commonly elevated in patients with chronic kidney disease (CKD) and the CLL-IPI has not been adjusted for compromised kidney function.

Methods: Between 2000 and 2022, newly diagnosed CLL patients not fulfilling criteria for immediate specific treatment were identified from the clinical database at a tertiary care center in Innsbruck, Austria. TTFT was stratified according to the CLL-IPI and CKD (GFR < 60 ml/min). B2M plasma levels were compared in CKD and non-CKD patients. In CKD patients with elevated B2M plasma levels (> 3.5 mg/L), the CLL-IPI was reviewed to check if elevated B2M plasma levels led to a higher CLL-IPI risk category.

Results: Our cohort included 299 CLL patients with a median age at diagnosis of 66 years (range: 32 – 88) and a female-to-male ratio of 1:2. CKD was evident in 15% of patients. CLL-IPI risk groups were balanced among patients with and without CKD (low: 34% versus 38%, intermediate: 44% versus 40%, high: 16% versus 12%, very high: 6% versus 10%). With a median follow-up of 98 months (range: 2 – 360 months) 53.5% of patients eventually met criteria for specific CLL treatment. Median TTFT was 154 months in both patients with normal and decreased kidney function, whereas B2M plasma levels were significantly higher in CKD patients (B2M > 3.5 mg/L: 35.5% versus 9.3%, p < 0.05). Elevated B2M plasma levels led to a higher CLL-IPI risk category in 19.4% of CKD patients.

Conclusion: CLL patients with CKD and elevated B2M plasma levels at the time of CLL diagnosis may show similar TTFT as non-CKD patients with normal B2M plasma levels. Our results suggest that the predictive value of B2M plasma levels on TTFT in newly diagnosed CLL patients, particularly as a factor in the CLL-IPI, must be interpreted with caution in those with decreased kidney function.