German CLL8 Part 1

The German CLL8 trial by Hallek et al in today's Lancet is the most important CLL paper published for a decade. Why?

Like most chronic lymphoproliferative disorders, CLL will be treated with many, perhaps all, alternative therapies during the course of the disease. There have been many trials of therapy in CLL and many have shown that a new combination of agents produces higher response rates than its comparator. Indeed many have shown that the new combination produces longer remissions than what has gone before, but hitherto there has never been a trial that showed that the new combination made a patient live longer than if he had been treated with the comparator regimen - for the very reason that those relapsing after the lesser regimen could be switched to the greater and not suffer a poorer overall outcome.

Thus until now it has not really mattered which regimen you started with, and there was some merit to selecting one with fewer side effects in the hope that you might never have to proceed to a treatment with greater side effects.

This trial which looks at what happens when you add rituximab to FC clearly demonstrates that you live longer than if you don't. The extra life is both statistically and clinically significant, it is bought without serious side effects and although it is quite expensive, I fully expect that NICE with recommend it for all UK patients who fit into the right category.

This result was unexpected; so much so that overall survival was not the primary endpoint of the trial - progression-free survival was - but overall survival was a secondary endpoint. Rituximab as a single agent has a poor reputation in CLL and even the manufacturers were not that optimistic about the drug.

This is a very large trial with over 400 patients in each arm and it is so important that I am going to go through it slowly on this blog. I will deal with it in bite size chunks so that no-one will feel that it is too complicated to understand.