ASH 2017: Professor Michael Hallek on Molecular Evolution in CLL and Venetoclax Resistance
This is one of the few abstracts (#7011) on CLL at the 2015 American Society Clinical Oncology (ASCO) Annual meeting in Chicago. Abstracts at ASCO tend to focus more on solid tumor cancers and the “big four”: lung, breast, prostate and colon.
But these are important research abstracts and we will review some of them here over the next few months.
Idelalisib (aka CAL-101 and now Zydelig) is an approved oral targeted therapy that as the first in class PI3Kδ inhibitor that turns off pro-survival and anti-apoptotic (programmed death) signals allowing the CLL cells to slowly die.
But like most targeted therapy, idelalisib doesn’t get us to cure or for many even to a complete remission.
So to help improve our odds, especially in those of us with nasty disease, this trial adds in different old school chemo-immunotherapy protocols to tackle those difficult patients among us. The disease had come back in all enrolled in the trial and more that half had become resistant to therapy, with three out of ten having deletion 17p. A tough crowd to treat.
So what were the results?
I quote:
“Med(ian) overall PFS (progressive free survival) was 26.1 mos, 20.3 mos for pts with del17p/TP53 mut(ation), and 36.8 mos for pts without. Med OS for all pts or pts with del17p/TP53 mut was not reached. Estimated OS (overall survival) at 36 mos. was 73.1% for all pts, 57.3% for pts with del17p/TP53, and 78.3% for pts without.”
And what about the adverse events (AE)?
They are what we might expect:
“Most common and select AEs independent of causality (any Grade/Gr ≥ 3): diarrhea/colitis (52%/19%), pyrexia (45%/4%), cough (37%/1%), nausea (29%/1%), fatigue (32%/4%), pneumonia (23%/15%), dyspnea (22%/3%), rash (21%/4%), pneumonitis (4%/4%). AST/ALT elevation Gr ≥ 3 was seen in 12%.”
And the conclusion:
“Idelalisib in combination with chemoimmunotherapy shows a manageable safety profile without increased toxicities and has substantial clinical activity in heavily pretreated, refractory, and high-risk CLL including presence of del17p/TP53mutation.”
Without the idelalisib in the mix, the results for this group would be historically much, much worse.
With important trials such as this, we are learning what cocktails work and how to improve on them.
The research must and will continue.
Here is a link to the abstract (#7011) itself.
Brian Koffman 5/22/15
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