A few Key thoughts which I will try and keep bulleted. In summary these are very good results especially when you consider the study population
- please bear in mind this study is not a “typical” group of second line patients no doubt partly because at the time this was a new drug and so you tend to recruit more seriously Sick patients who’ve tried and failed other treatments when a drug is new. If you take ibrutinib firstline or after just one or two other treatments you may well do a lot better than the “average” patient in this study
-In addition about 80% of patients had at least one genetic marker of being “High risk” and in this context the results are really good.
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it’s also likely that most of these patients may not have been able to get Venetoclax if they failed ibrutinib as it would not have been available in the early years of the study. (Only seven patients were able to be treated with venetoclax when they relapsed)
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Half the patients were not still taking ibrutinib by 41months (this is what the median means) and by the end of six years 22% were still taking it.
-40% of ibrutinib patients had still not progressed at 60 months suggesting that perhaps relatively few patients progressed in the last two years (ie if you have got to four years without progression you were likely to remain ok for the last two) This is the data shown in the photo attached.
-50% (the median) of ibrutinib patients had progressed by 41 months. Remarkably this was the same for patients with high risk genetics. If anything there is a trend towards the low risk doing less well but there were far too few patients for this to be confirmed as a real feature.
-The majority of patients who had only taken 1 treatment before ibrutinib had not progressed by the end of the study period
-The estimate of the point when half the ibrutinib patients remained alive was 67.7 months BUT the confidence of this estimate crossed the end of the study (ie the real figure might be longer than this six year study). Also please consider that the vast majority of these patients had high risk genetics and had also been heavily pre treated before ibrutinib.
-The more prior treatments patients had previously had the less likely they were to have not progressed (with 50% of patients who’d had five treatments or more having progressed by 27 months)
-Ibrutinib clearly saved lives compared to the comparator drug but in good news for those of us not taking ibrutinib first-line (and perhaps also delaying it beyond venetoclax in some cases) even in this heavily pre-treated group the mortality difference almost entirely evaporated since so many of the comparator patients were able to take ibrutinib later into the study when needed.
- 10% of this group of high risk patients progressed to a Richters transformation the majority of which occurred in the early years suggesting perhaps that for many patients the mutation had already occurred before starting ibrutinib.
—annoyingly fatigue doesn’t seem to have been measured directly but 65% of patients reported an improvement in quality of life and since as we all know fatigue is a huge downer then surely many patients must have been seeing an improvement.
-Over up to 71 months of treatment, commonly reported grade ≥3 adverse events included neutropenia (25%), thrombocytopenia (10%), anemia (9%), pneumonia (21%), hypertension (9%), urinary tract infection (7%), diarrhea (7%), and atrial fibrillation (6%), 19 patients (10%) in the ibrutinib arm experienced major hemorrhage. The prevalence of any grade ≥3 AEs with ibrutinib decreased after the first year and remained stable over the rest of the study
Infections of grade ≥3 occurred in 87 patients (45%) in the ibrutinib arm.
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To conclude ibrutinib did a great job of controlling the CLL of a group of patients who were high risk and heavily pre treated. The average patient on ibrutinib today might very reasonably expect to do better then the average patient in this study. And we should note that in the years that this study had been recruiting treatment for CLL has improved dramatically with a recognition even in most government funded healthcare systems that repeated exposure to chemotherapy is not the best way to control CLL as it encourages clonal evolution towards more aggressive forms of the disease, and this study shows that even these aggressive forms can be treated by ibrutinib.
There are also already other selective new treatments that can be used after (or before) ibrutinib and so again we can reasonably expect even better outcomes in the future.
