Prognostic Value of CLL-IPI Diminished in Targeted Therapy Era

A new evaluation of the prognostic impact of the Chronic Lymphocytic Leukemia International Prognostic Index (CLL-IPI) revealed that its impact appears diminished in predicting overall survival in the era of targeted drugs.

The CLL-IPI “combines pretreatment genetic, biochemical, and clinical parameters into a prognostic model for overall survival (OS), discriminating four prognostic subgroups. However, the score was established in patients with CLL treated first-line with chemoimmunotherapy, which is less efficacious in patients with CLL and high-risk features,” study researchers explained. More recent targeted therapies have improved outcomes for patients with CLL, even those considered poor risk.

Researchers evaluated the CLL-IPI using data from a group of patients with CLL treated with first-line targeted drugs (991 patients) or chemoimmunotherapy (1,256 patients).

The three-year progression-free survival (PFS) for patients treated with targeted drugs was 96.5% for CLL-IPI low, 87.5% for intermediate, 82.4% for high, and 78.7% for very high. There were significant differences between PFS for consecutive risk groups for intermediate versus low (P=.002) and high versus intermediate (P=.048), but not for high compared with very high.

In comparison, the three-year OS rates were 100% for CLL-IPI low, 96.0% for intermediate, 93.9% for high, and 89.4% for very high. However, there were no significant differences between consecutive risk groups.

Risk factors for PFS, such as β2-microglobulin, IGHV mutational status, and TP53 status, and for OS, such as β2-microglobulin, age, Binet stage, and TP53 status, retained their prognostic value among the group of patients treated with targeted drugs.

Use of CLL-IPI in patients treated with chemoimmunotherapy was fully validated, the researchers noted.

“Our analysis of a pooled data set of clinical phase 2 and 3 trials suggests that the CLL-IPI maintains its prognostic value in predicting outcomes for PFS in patients treated first-line with targeted drugs,” the researchers wrote. “However, with a median observation time of 40 months, the impact of the CLL-IPI was diminished in predicting survival, underscoring the potential of these targeted therapies to improve outcomes across different risk groups.”

Reference

Langerbeins P, Giza A, Robrecht S, et al. Reassessing the Chronic Lymphocytic Leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024. doi:10.1182/blood.2023022564