Investigators recently reported the development of an international prognostic score (IPS) that predicts the likelihood of treatment requirement in patients with early, asymptomatic chronic lymphocytic leukemia (CLL), according to results published in Blood. The model may be useful not only in clinical management, but also in the design of clinical trials.

Due to the heterogeneous disease course seen in patients with early-stage CLL, many patients may not require treatment for years; therefore, a team of international investigators conducted a multicenter retrospective observational study ( Identifier: NCT03436524) to predict the probability of time-to-first treatment (TTFT) in this subset of patients with asymptomatic disease.

To create and validate the IPS-E model, the team acquired datasets from 4933 patients with early-stage CLL from 11 international cohorts. They performed both univariate and multivariate analyses on clinical, laboratory, cytogenetic, and gene mutation data to identify covariates correlated with TTFT.

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The presence of unmutated IGHV genes, absolute lymphocyte count >15×109/L, and presence of palpable lymph nodes were consistently and independently correlated with TTFT; the IPS-E was the sum of these 3 covariates. The patients could then be separated into low-risk (score 0, longest TTFT), intermediate-risk (score 1, intermediate TTFT) and high-risk groups (score 2-3, shortest TTFT).

The team then validated the IPS-E accuracy using data from 10 cohorts (9 staged by the Binet system and 1 cohort staged by the Rai system). The ability of the IPS-E to discriminate TTFT (c-index) was 0.74 in the training series and 0.70 in the validation series.

According to the results of a meta-analysis of the training and validation data, the estimated 5-year cumulative risk of treatment start was 8.4% for low-risk patients, 28.4% for intermediate-risk patients, and 61.2% for high-risk patients.

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The authors noted that the risk of biases related to the timing of scheduled evaluations and premature censoring could not be overlooked, and they believed that the IPS-E warrants prospective evaluation and can be improved with additional patient data.

“The IPS-E could help physicians, medical care providers, and health authorities in their strategies and resources allocation,” wrote the authors. “Likewise, such a prognostic model could be useful to design clinical trials for high-risk early-stage CLL patients, an issue that has gained momentum due to the availability of effective small molecules with manageable toxicity.”

Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Condoluci A, Terzi di Bergamo L, Langerbeins P, et al. International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia [published online April 8, 2020]. Blood. doi: 10.1182/blood.2019003453