Is there anyone on here who has been identified to have 'Notch1 Geno mutation'?
Started Alcalbrutinib in February and suffered horrendous headaches and sickness to begin with. After 2 visits to the Hospital I was taken off all medication except Acalabrutinib and had my first monthly checkup last Thursday and now have started Allopurinol but told if I had any problems to stop it immediately and thankfully to date things are going OK.
However one of the blood tests taken has shown that I have 'Notch1 Geno mutation' which has apparently taken me from 'Excellent' to 'Low' now.
My Consultant couldn't tell me much information on the day but hopefully I'll know more when I see him on the 14th April.
Written by
BethIlia
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Do you know if your markers are an unmutated Trisomy 12 +cd38?
I remember twelve years ago when I first was diagnosed, they were talking about Notch 1. The test was hard to get and done by schools of medicine or trials.
When BTK treatments started I didn't hear them mentioned. I was always worried I had a Notch 1 because I was T 12 +cd38.
No all he said was Notch1. He did say the only information he could get before he saw me was from 10-15 years ago. He'll probably give me more info in April when I see him but at least now I can ask the question. Thank you.
Not sure if this is useful, but Dr. Kipps discusses Notch1 in this short video from 2015: onclive.com/view/role-of-no...
There's also this piece from 2019. "A mutation on the NOTCH1 gene was shown to be an independent predictive factor for the reduced efficacy of ofatumumab (Arzerra), a human monoclonal CD20 antibody, in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to study results presented at the 2017 International Workshop on Chronic Lymphocytic Leukemia. The impact of additional mutations, including TP53 and SF3B1, were also noted."onclive.com/view/predictive...
The recently concluded 2nd ESH Translational Research conference on Chronic Lymphocytic Leukemia (ESH CLL), 2022 had a session on NOTCH1 mutation in CLL.
During that conference, John Allan, MD, Weill Cornell Medicine, New York, NY, recorded a brief video on the topic for VJHemOnc.
He explains that, although this mutation has traditionally been associated with more aggressive CLL and earlier times to first treatment, more recently, promising outcomes have been seen in NOTCH1-mutated patients treated with Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors.
“All current evidence shows that when you use novel therapeutics like BTK inhibitors and BCL2 inhibitors etc, this poor risk prognosis seems to be overcome and those patients with NOTCH1 mutations seem to be doing just as well as everyone else and it’s somewhat lost its prognostic significance in identifying high risk CLL once treatment starts.”
He goes on to explain that the mutation can be associated with other higher risk CLL factors that mean patients with it still require close monitoring.
Dr Byrd told us exactly the same thing. My husband is 13q deleted, unmutated and Nothch 1 +ve. Diagnosed 9 years ago and now on Acalabrutinib for almost 2 yrs. Previously on an ibrutinib clinical trial for 2 yrs and then when the trial ended ,treatment free for almost 2 yrs before starting Acala.
I'm also Notch 1 positive, 11q deleted, unmutated, Trisomy 12 but I have done well 5+ years on Acalabrutinib. Hope you adjust and can stay on the meds. My profile is considered Intermediate to High Risk but understand that even Intermediate to High Risk profiles do well on the BTK inhibitors.
I have unmutated CLL and notch 1, trisomy 12 although negative for cd 38. The notch 1 particularly scares me so I do a lot of research and have watched all the videos I can find. My biggest concern is the increased risk of Richters transformation associated with trisomy 12 Notch 1. I was diagnosed less than 2 years ago and so far stage 0. I am monitored every 3 months. There is some talk about earlier treatment to prevent Richters but no data so far to prove this.
I also am Tri 12, Notch 1. I was diagnosed 9 years ago with CLL and later asked to be tested for Notch 1 (2016). My oncologist calls me high risk but I had almost 4 years W&W, 5 1/2 good years on Ibrutinib, from which I just relapsed, and have begun Venetoclax, which is working.
As Hail Mary and Dori Zett said, the new medications work. I live a normal life and bless the researchers!
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Trisomy 12
tp53 mutation
13Q Deletion and ATM Mutation 
CLL / P17 with Mutation
2nd Update on Possible Richters Transformation
