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A study in Cancer compared the accuracy of five risk scores for time to treatment in CLL, including the IPS-E, CR0, AIPS-E, CLL-IPI, and Barcelona-Brno.

A study published in Cancer compared the accuracy of five risk scores in patients with untreated chronic lymphocytic leukemia (CLL):

• International Prognostic Score for Asymptomatic Early-Stage CLL (IPS-E)
• CR0
• Alternative IPS-E (AIPS-E)
• International Prognostic Index for CLL (CLL-IPI)
• Barcelona-Brno

“These scores predict time to first treatment (TTFT) in a high proportion of patients, but some patients are still misclassified,” wrote Miguel Arguello-Tomas, MD, and colleagues.

The retrospective study included 781 patients (median age, 66.7 years) from three academic centers in Spain. There were no significant differences in clinical and biological characteristics at baseline.

As for mutational status, 37.3% of patients had unmutated IGHV, 8.3% had del(11q), and 9.2% had TP53 aberrations. Of the 99 patients (12.7%) who had IGHV stereotypic subsets of special interest, 15 (1.9%) were subset #1, 18 (2.3%) were subset #2, 73 (9.3%) were subset #4, and 26 (3.3%) were subset #8.

Validating Risk Scores

Calibration, as measured by Hosmer-Lemeshow goodness of fit, was similar and good for the risk scores (P=0.98). Using Harrell’s C Index, the researchers determined that discriminatory values were high for all risk scores (c=0.78 for IPS-E, c=0.79 for CR0, c=0.77 for AIPS-E, c=0.78 for CLL-IPI, and c=0.79 for Barcelona-Brno). Akaike information criterion scores were similar among IPS-E (840), CR0 (847), AIPS-E (842), and Barcelona-Brno (844), but CLL-IPI had the lowest score (441), indicating highest predictive accuracy.

Weighted kappa analysis showed substantial concordance (κ=0.61-0.8) between the IPS-E, CR0, AIPS-E, and Barcelona-Brno scores; substantial concordance between the Barcelona-Brno and CLL-IPI scores; and moderate concordance (κ=0.41-0.6) between the CLL-IPI and IPS-E, CR0, and AIPS-E scores.

A total of 269 patients (34.4%) were categorized in the same risk category across all five scores.

“The different risk scores were successfully validated in our series and reproduced the low-, medium-, and high-risk groups for TTFT,” wrote Dr. Arguello-Tomas and colleagues. “The risk groups maintained their prognostic value when calculated as a cumulative incidence with competitive events (eg, death without the start of therapy).”

IGHV Mutational Status & TTFT

The median TTFT was 3.9 years for unmutated IGHV but was not reached for mutated IGHV (P<0.001). The researchers also found that IGHV mutational status significantly correlated with TTFT.

Patients with IGHV subsets #1, #2, and #8 had similar TTFT when compared with patients with unmutated IGHV. Additionally, patients with subset #4 had similar TTFT to those with mutated IGHV. Those with subset #2 had similar TTFT regardless of IGHV mutational status (P=0.54).

The researchers noted that some information to determine risk scores was missing due to the retrospective nature of the study. Because the study included patients from academic referral institutions, the results may not be applicable to community centers.

“IPS-E, CR0, AIPS-E, CLL-IPI, and Barcelona-Brno are robust risk scores to predict TTFT,” the researchers concluded. “We suggest that the IGHV subset #2 appears to be useful to improve the accuracy of the risk scores. IPS-E, CR0, CLL-IPI, and Barcelona-Brno are also able to predict OS.”