Re: Re: del 11q

[Guest guest]

Dr Furman has kindly drawn my attention to a paper I had missed. At last

year's ASH in the education session there was a mini-review of treatment for

del 11q. The authors looked at three trials of CLL treatment which had

patients with and without alkylating agents in the mix. they were the LRF CLL4

trial, the German CLL study and the E2997 study. This is what they say

about them:

In these three trials, patients with deletion of 11q had shorter PFS. In

the Leukemia Research Foundation CLL4 trial and the German CLL study, del(11q)

patients had statistically significant longer PFS or higher response rates

when treated with FC compared with their counterparts treated with

fludarabine alone. Additionally, although PFS in del(11q) patients treated with

FC

appeared longer compared with similar patients treated with fludarabine in the

E2997 trial, it did not reach statistical significance after approximately

3 years of follow-up.

In summary, there is evidence from a subgroup analysis of randomized

clinical trials that the addition of alkylating agents, in particular

cyclophosphamide, to fludarabine is associated with superior response rate and

longer

PFS in patients with the 11q deletion (Grade 1A). While data on response

duration and overall survival still indicate that this group of patients has

an inferior outcome compared with patients with favorable genomic

abnormalities.

These data are impressive in the sense that FC is better than F for all

sorts of CLL except del 17p, but of responders, del 11q still does worse than

the others and it was very noticeable in the LRF CLL4 trial that the del

11q group relapsed early. What was remarkable about the German CLL8 trial was

that FCR was so much better than FC and del 11q was no longer an adverse

prognostic marker for the FCR arm. What we don't know is whether FR would

have been as good and to use the CLL4 data to insist of FCR rather than FR is

premature. I rather suspect that FCR might be better, though in the long

run the risk of secondary MDS might give us pause.

Terry Hamblin MD