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Exploring Prognostic Value of Genetic Testing at Diagnosis in Chronic Lymphocytic Leukemia
Findings from a recently published study confirmed the prognostic value of immunoglobulin heavy chain (IGHV) mutational status at diagnosis for overall survival (OS) and time to first treatment (TIFT) in patients with chronic lymphocytic leukemia (CLL), including early stages. Findings also indicated the possible role for molecular and mutational analysis at diagnosis in future prospective studies (Diagnostics 2022, 12, 1802. https://doi.org/10.3390/diagnostics12081802).
Alexia Suarez-Cabrera, MD, Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas, Spain and colleagues conducted a retrospective non-interventional study in which a total of 217 adults with CLL, of which 123 (57.1%) were men and 94 (42.9%) women. The average age at diagnosis was 70 years [36–91 years].
The objective of the study was to examine the clinical, biochemical (β2-microglobulin values), cytogenetic (deletion of 17p, 11q, 13q and trisomy 12 by FISH) and molecular (TP53 and IGHV mutational state) characteristics at diagnosis of a series of 217 patients diagnosed with CLL at their center and ascertain their impact on prognosis.
The IGHV mutational status of 109 patients was obtained at diagnosis, of which 41 (37.6%) were non-mutated and 68 (62.4%) were mutated, comparable to what has been documented in the literature.
After 24 months of follow-up, 92.6% of patients were alive in the low/intermediate CLL International Prognostic Index (CLL-IPI) subgroup compared to 76.9% in the high CLL-IPI subgroup, while at 72 months the percentages were 83.4% vs. 0%, respectively.
With regards to the variables incorporated in the CLL-IPI (IGHV-unmutated, del(17p) and/or TP53 mutations, age over 65 years and high β2-microglobulin serum levels), high β2-microglobulin levels (>3.5 mg/L), IGHV-unmutated status, and age over 65 years were linked with worse OS in the univariate analyses.
Results revealed that multivariate analyses identified prognostic variables for OS and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0–2/Binet A), respectively. Moreover, unmutated IGHV was correlated with shorter OS and TTFT, even for early-stage patients and lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis.
The authors wrote, “Our study confirmed that the CLL-IPI variables of an age of 65 years or older, advanced Rai stage and IGHV-unmutated, but not β2-microglobulin value, had an independent impact on worse overall survival,” adding, “Our key result was that IGHV-unmutated was an independent predictor for TTFT, confirming recent publications of scores for early-stage CLL.”
