This article was originally published by Healio

A novel prognostic tool appeared to predict the need for treatment among patients with asymptomatic, early-stage, chronic lymphocytic leukemia, according to research published in Blood.

“CLL is an indolent disease that is treated only if symptomatic. Currently, between 70% and 80% of newly diagnosed [patients with CLL] are asymptomatic and therefore are offered a wait-and-see approach to management consisting of regular visits every 3 to 12 months. However, this approach is not easily accepted by patients, who often ask whether, when and how they will be treated,” Davide Rossi, MD, researcher at Oncology Institute of Southern Switzerland, told Healio. “So far, the eventual disease course cannot be predicted for patients after they have been offered wait and see, which in turn causes anxiety and uncertainty. Having a tool that accurately forecasts leukemia course will help patients in planning their life with the disease.”

Rossi and colleagues developed and tested the international prognostic score, IPS-E, to predict time to first treatment among 4,933 patients with early-stage, asymptomatic CLL included in 11 global cohort studies.

Among a training cohort of 333 patients, investigators observed three consistent and independent covariates that appeared associated with time to first treatment: unmutated IGHV genes, absolute lymphocyte count greater than 15 x 10⁹/l and the presence of palpable lymph nodes. They used data from this cohort to develop a prognostic score with each factor counting as one point. Patients with zero factors were considered at low risk for requiring treatment within the first 5 years of diagnosis, those with one factor were considered at intermediate risk, and those with two or three factors were considered at high risk.

Investigators validated the score in nine cohorts staged by the Binet system and in one study staged by the Rai system. They observed C-index scores of 0.74 in the training series and 0.7 in the aggregate of validation series.

Overall, approximately 30% of patients were categorized as low risk, 35% as intermediate risk and 35% at high risk.

Moreover, meta-analysis of the cohorts showed 5-year cumulative risk for treatment initiation of 8.4% among patients considered low risk, 28.4% for those in the intermediate-risk group and 61.2% for those at high risk.

“In a time where the treatment paradigm of asymptomatic CLL may change if a survival benefit is proven by early intervention with novel agents, our international prognostic score could help in defining the early-stage population where treatment can be appropriate,” Rossi said. “Moreover, it could be helpful for the treating physician to better allocate medical resources, such as deciding on the interval between clinical assessments according to risk group. Health care professionals will be supported in the discussion while explaining CLL to patients — many of whom have never heard about the rare tumor. Physicians can also safely plan and advise in advance the proper timing of surveillance visits according to the predicted risk of leukemia progression.”

The international prognostic score warrants prospective evaluation, according to Rossi, and can be regarded as a building block on which newly discovered independent outcome predictors for patients with early-stage CLL could be added.

“In this sense, a prospective study could be designed to further assess and eventually strengthen this prognostic tool,” Rossi said.

For more information:

Davide Rossi, MD, can be reached at Oncology Institute of Southern Switzerland, Via Ospedale, 6500 Bellinzona, Switzerland; email: davide.rossi@eoc.ch.