Conference Coverage: CLL-IPI: A New and Improved Staging System for CLL?

CHICAGO—In a recent study examining the strength of prognostic markers for patients with chronic lymphocytic leukemia (CLL), researchers believe they have found an internationally applicable prognostic index for patients with CLL. Called CLL-IPI (International Prognostic Index), the newly developed scoring system represents a collaboration between multiple international study groups.

Nadine Kutsch, MD, from the University Hospital of Cologne, in Germany, presented the new CLL-IPI system during a presentation at the 2015 ASCO Annual Meeting. “In times of novel therapies and improved prognosis for patients with CLL, the traditional staging system developed by Rai and Binet more than 30 years ago no longer discriminate enough,” Dr. Kutsch said. “In order to allow better information on survival, a number of new prognostic markers has been introduced, but there is no broadly applicable system integrating all these markers.” Furthermore, many of these prognostic tests rely on complex (and costly) molecular and biologic assays and are not available to all patients with CLL.

CLL-IPI, which was developed through analysis of 26 prognostic factors, could serve as a simple, reliable, and easily applicable method of risk stratification for patients with CLL.

The international group of researchers collected data from eight phase III clinical trials from France, Germany, the United Kingdom, the United States, and Poland. In total, the studies included 3,472 treatment-naïve patients at both early and advanced CLL stages (median age, 61 years; range, 27-86 years). Patients were followed for a median of 80 months.

The full analysis set was randomly divided into training and internal validation datasets (training: n=2,308, 67%; internal validation: n=1,164, 33%). The study’s model was externally validated in a third dataset that included 845 newly-diagnosed CLL patients from the Mayo Clinic in Rochester, Minnesota; these patients’ had a mean age of 62 years (range, 25-89 years) and were observed for a median of 63 months.

Of the 1,192 patients from the training dataset (52%), five independent predictors for OS were identified: age, clinical stage, del(17p) and/or TP53 mutation status, IGHV mutation status, and ß2-microglobulin (B2M) level. Each variable was then assigned an individual weighted grade (TABLE).

TABLE. Multivariate analysis of independent predictors for overall survival in the CLL-IPI system

Variable

Adverse factor Coefficient Hazard ratio Grading
Age

>65 years

0.555 1.7

1

Clinical stage

Binet B/C or Rai I-IV

0.499 1.6

1

Del(17p) and/or TP53 mutation

Deleted and/or mutated

0.665 2.0

4

IGHV mutation status

Unmutated

0.941

2.6

2

B2M level, mg/L

>3.5 mg/L 1.442 4.2

2

Adding all these factors together results in a prognostic score ranging from 0-10, with four different risk groups: low (score 0-1), intermediate (score 2-3), high (score 4-6), and very-high (score 7-10). Patients in these four groups had significantly different rates of five-year overall survival (95% CI 0.69-0.76; p<0.001):

  • Low-risk patients (n=340): 93.2 percent
  • Intermediate risk (n=464): 79.4 percent
  • High risk (n=326): 63.6 percent
  • Very-high risk (n=62): 23.3 percent

The results “were nicely confirmed” by the internal validation dataset as well as in a subgroup analysis of Rai stages, Dr. Kusch noted. “Applying the analysis to the external validation data from the Mayo Clinic cohort, we found a high replication of the developed prognostic index – across all Rai stages.” Five-year overall survival rates were 94 percent, 91 percent, 68 percent, and 21 percent among the low to very-high risk groups (95% CI 0.74-0.85; p<0.001).

How would the CLL-IPI score be applied in the clinic? Dr. Kutsch and colleagues provided the following treatment recommendations:

  • Low: Do not touch (watch-and-wait approach)
  • Intermediate: Do not treat (except when the patient is symptomatic)
  • High: Treat (except when the patient is asymptomatic)
  • Very-high: Treat in experimental protocol or with non-cytotoxic drugs if possible (no chemotherapy or chemoimmunotherapy)

“[The use of CLL-IPI] leads to an advancement of the classic clinical staging systems and a refinement in prognosis for CLL. “Importantly, this is a modular score,” Dr. Kutsch noted, meaning that any new prognostic marker could easily be validated and incorporated into the score.


Source: Kutsch N, Bahlo J, Byrd JC, et al. The international prognostic index for patients with CLL (CLL-IPI): An international meta-analysis. Abstract #7002. Presented at the American Society of Clinical Oncology 2015 Annual Meeting, Chicago, Illinois, May 30, 2015.

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