Prognostic factors identify 3 risk groups in the LRF CLL4 trial, independent of treatment allocation

May 30, 2010

Blank(Haematologica 2010, 10.3324/haematol.2010.025338)

Prognostic factors identify 3 risk groups in the LRF CLL4 trial, independent of

treatment allocation

Oscier1,*, Wade2, Zadie 1, Alison Morilla3, Giles Best1, Sue

s2, Else3, Estella Matutes3, Catovsky3

1 Royal Bournemouth Hospital;

2 Clinical Trial Service Unit, Oxford;

3 The Institute of Cancer Research

* Corresponding author; email: d.oscier@...

ABSTRACT

Background: Many prognostic markers have been identified in chronic lymphocytic

leukemia, but opportunities have been few to assess their relative importance in

a large randomized trial. The aim of this study was to determine which markers

best predict outcome in patients requiring treatment.

Design and Methods: A broad panel of clinical and laboratory markers, measured

at randomization in patients entering the LRF CLL4 trial, was assessed with

respect to treatment response, progression-free and overall survival, at 68

months median follow-up.

Results: Using the factors identified as independent predictors for

progression-free survival, patients were subdivided into three risk groups: 6%

poor risk with known TP53 loss >10%; 72% intermediate risk without TP53 loss

(<10%) and with at least one of: unmutated IGHV genes and/or IGHV3-21 usage, 11q

deletion, ß-2 microglobulin > 4mgs/l; 22% good risk (with none of the above and

mutated IGHV genes). Five-year progression-free survival was 0%, 12% and 34%,

respectively and 5-year overall survival was 9%, 53% and 79%, respectively,

(both p<0.00005 independent of treatment allocation). In the intermediate risk

group 250 patients, with data for all three risk factors, were further

subdivided into intermediate low (one risk factor) or intermediate high (2 or 3

risk factors). Five-year progression-free survival was 18% and 7% (p= 0.0001)

and 5-year overall survival was 68% and 40% (p< 0.00005) respectively.

Conclusions: This study demonstrates the role of biomarkers in prognosis and

shows that, in patients requiring treatment, disease stage may no longer be an

independent predictor of outcome. If validated independently, the risk groups

defined here may inform the design of future trials in chronic lymphocytic

leukemia.

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