Association of gene mutations with time‐to‐first treatment in 384 treatment‐naive chronic lymphocytic leukaemia patients

[Jm954]

First published: 26 June 2019 in BJH - full paper behind a paywall unfortunately

This study correlated somatic mutation results and known prognostic factors with time‐to‐first treatment (TTFT) in 384 treatment‐naïve (TN) chronic lymphocytic leukaemia (CLL) patients to help determine disease‐specific drivers of early untreated CLL.

CLL DNA from either peripheral blood or bone marrow underwent next generation targeted sequencing with a 29‐gene panel. Gene mutation data and concurrent clinical characteristics, such as Rai/Binet stage, fluorescence in situ hybridisation (FISH), ZAP70/CD38, karyotype and IGHV mutation, status were analysed in univariable and multivariable analyses to identify associations with TTFT. TTTF was defined as time from diagnosis to initial treatment.

In univriable analyses, mutated ATM (P < 0·001), NOTCH1 (P < 0·001) and SF3B1 (P = 0·002) as well as unmutated IGHV (P < 0·001), del(11q) (P < 0·001) and trisomy 12 (P < 0·001) by hierarchal FISH and advanced Rai (P = 0·05) and Binet (P < 0·001) stages were associated with shorter TTFT.

Importantly, del(17p), mutated TP53 and complex karyotype were not associated with shorter TTFT.

In a reduced multivariable analysis, mutated ATM (P < 0·001) and unmutated IGHV status (P < 0·001) remained significant, showing their importance in early leukaemogenesis.

High‐risk prognostic markers such as del(17p), mutated TP53 and complex karyotype, were not correlated with TTFT, suggesting that these abnormalities have limited roles in early disease progression but are more important in relapsed CLL.

onlinelibrary.wiley.com/doi...

Jackie

[Spacee]

Thanks Jackie. Not always easier to absorb but I think I get the gist of these reports!

Linda

[Jm954 Administrator in reply to Spacee]

The only thing to remember was ATM mutated (as in 11q del) and unmutated IGHV were significantly associated with a reduced time to first treatment. The others (17p etc) appeared to be only important at relapse.

Not that we can do anything about it!

Jackie

[Smakwater in reply to Jm954]

Good parallel to the recent EugeneL2 post.

cancertherapyadvisor.com/ho...

JM

[bachplayer13 in reply to Jm954]

so if i was told that i have an atm mutation does that mean or imply that i am 11q deleted also? confused about that!

[camper2 in reply to bachplayer13]

I am seeing my Onc on Monday to discuss my FISH results. He rang me and said I was 11q so that I do know. I will try to remember to ask him your question and let you know - if some of the others on here don’t reply before then!

[DriedSeaweed]

Sometimes the paywall can be high enough my library says they cannot afford it.

I tried requesting a copy on researchgate but to no avail thusfar.

Sometimes if we wait a year or so they can become more accessible.