Friday, October 08, 2010

German CLL8 part 12.

This is the final posting on CLL 8 and I just want to make the final point that the usual prognostic factors that we have known about for up to ten years have turned up trumps again in this trial.

Click to enlarge. These prognostic factors were originally discovered to predict prognosis in retrospective series, but they have been tested regularly in prospective studies and almost always they have been useful to predict what will happen in trials. The stand out prognostic factor is del 17p, and although it only represents about 5% of patients, these patients do so badly on either FC or FCR that they have to be excluded from these treatments. The other important message is that del 11q, always thought to be a bad deal, loses its grim future if FCR is used first line.

A high Beta-2 microglobulin is now a useful predictor of shorter pfs and OS and unmutated IGVH genes a useful predictor of a shorter remission, though not of overall survival yet in a multivariate analysis. We will have to watch how that pans out with longer follow up. As might be expected, a poor performance score leads to a shorter survival than a good one. Serum thymidine kinase levels are only measured in Germany, so we can't comment on their usefulness elsewhere. They require a radioassay. Beware of anyone offering you this test as an ELISA.

In conclusion:
* The addition of rituximab to FC first line therapy improves the outcome of patients with advanced, symptomatic CLL with regard to
* Response rates (CR, ORR, MRD)
* Progression-free survival
* Overall survival

* Achieving a CR produces longer survival.

* This is the first randomized trial to demonstrate that the choice of first line therapy improves the natural course of CLL.


Anonymous said...

Thank you for 12 very informative posts on CLL8. Your insight, as usual, added a very valuable perspective. Thanks also to the wonders of DEX in giving you the stamina to read, digest, and post.

Burke said...


Am I correct in recalling that there have been other studies indicating that MRD negative remissions last considerably longer than other CR's?

Can those with MRD neg remissions reasonably expect a longer PFS and OS?

Terry Hamblin said...