August 2015, Vol 4, No 4

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New CLL-IPI Scoring System Validated as Clinically Applicable


Traditional staging systems for chronic lymphocytic leukemia (CLL), such as Rai and Binet, need to be updated in the current era of more effective therapies. A group of investigators has developed a CLL-IPI (International Prognostic Index) scoring system that combines genetic risk factors with clinical stage, age, and ?2-microglobulin into a clinically applicable prognostic score for CLL patients. Moreover, the CLL-IPI discriminates between prognostic groups and can inform treatment decisions.

“The traditional staging system developed more than 30 years ago for CLL does not discriminate enough any more. There are newly discovered prognostic markers, but no system integrates all these markers. We report on an international effort to develop a comprehensive score,” said Nadine Kutsch, MD, for the International CLL-IPI Working Group. Dr Kutsch is at the Center of Integrated Oncology Cologne Bonn and the University of Cologne in Cologne, Germany.

The full analysis set relied on data from 8 phase 3 trials in Europe that included 3472 treatment-naive patients in various stages of CLL. Median age was 61 years, and median observation time was 80 months. The full analysis set was randomly divided into training (n = 2308) and internal validation data sets (n = 1164). Once the new system was developed, it was externally validated prospectively in a third data set comprising 848 newly diagnosed patients treated at the Mayo Clinic in Rochester, MN; median age was 62 years, and 39% had received treatment.

A multivariate analysis identified 5 independent predictors for overall survival (OS): TP53 status and/or del(19p), IGHV status, ?2-microglobulin level, clinical stage, and age. A prognostic score was developed ranging from 0-10, and 4 different risk groups were derived: prognostic score of 0-1, low risk; prognostic score of 2-3, intermediate risk; prognostic score of 4-6, high risk; and score of 7-10, very high risk. These 4 risk groups, respectively, had different OS at 5 years: 93%, 79%, 64%, and 23% (P <.001). This model was confirmed on the internal validation data set, and then on the Mayo set, with 5-year OS of 97%, 91%, 68%, and 21%, for the low-risk to the very high-risk groups, respectively.

Dr Kutsch outlined the clinical application of the CLL-IPI system as follows: for low-risk patients, watch and wait; for intermediate-risk patients, treat only if symptomatic; for high-risk patients, treat except if they are asymptomatic; and for very high-risk patients, treat with experimental approaches.

“The CLL-IPI is an important contribution to the field of CLL. The score is easily applicable and can be applied prospectively,” said Dr Kutsch.

“Weighted scoring helps clarify the impact,” said Wendy Stock, MD, University of Chicago, IL, who discussed this abstract.

Genetics - August 24, 2015

Considerations in Genetic Testing

Now that new tests are changing the landscape of genetic testing, challenges are emerging in communicating results to patients, according to presenters at an education session on “Genetic Testing in 2015: Who Owns the Data, How Do You Return Results, and Other Clinical Dilemmas.” Multigene panels can now be offered [ Read More ]

Uncategorized - August 24, 2015

Combination Targeted and Immunotherapy Feasible in Advanced Melanoma

One of the burning questions about the new agents available to treat melanoma is how best to combine and/or sequence them. A phase 1 study showed the feasibility of combining a BRAF inhibitor and a MEK inhibitor plus a programmed death-1 ligand 1 (PD-L1) inhibitor (MEDI4736). These 3 agents can [ Read More ]