ASH 2023 | Ibrutinib treatment for CLL does not increase the incidence of Richter’s transformation
Paul Hampel, MD, Mayo Clinic, Rochester, MN, discusses the impact of introducing ibrutinib treatment for chronic lymphocytic leukemia (CLL) on the incidence of Richter’s transformation (RT). Using the prospectively maintained Mayo Clinic CLL database, it was determined that there was no significant difference in RT incidence before and after the introduction of this treatment, which marked the start of the novel targeted era in CLL. Although initial concerns speculated ibrutinib could increase the risk of RT, this data concludes this is not the case. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (edited for clarity)
What we know about Richter’s transformation and the incidence of this, or prevalence, mostly comes from retrospective series or sometimes from clinical trial cohorts, and we see ranges that are somewhat all over the place. What we tried to do in this study, was take a look at patients in the Mayo Clinic CLL database, which is prospectively maintained, and looking at a cohort of over 3000 patients from the time of diagnosis going forward to get a better understanding of what the the natural history and the true incidence rate may be...
What we know about Richter’s transformation and the incidence of this, or prevalence, mostly comes from retrospective series or sometimes from clinical trial cohorts, and we see ranges that are somewhat all over the place. What we tried to do in this study, was take a look at patients in the Mayo Clinic CLL database, which is prospectively maintained, and looking at a cohort of over 3000 patients from the time of diagnosis going forward to get a better understanding of what the the natural history and the true incidence rate may be.
We looked at patients who were diagnosed with their CLL prior to February 2014, compared to those in February 2014 or later, which was the approval date for ibrutinib, and kind of designated these as the pre-novel agent or pre-targeted agent era versus the novel agent or targeted agent era to see, are we seeing a difference in the incidence of Richter’s now compared to patients in a chemoimmunotherapy or pre novel agent era?
The five year rate of Richter’s transformation incidence was 3.7% in the pre-novel agent era, compared to 1.9% at five years in the novel agent or targeted agent era. This was a trend, and you can see the curves for yourselves, there’s a difference there but not statistically significant, but certainly appears to be a signal that there may be a lower rate, at least in that window, of Richter’s transformation in the current era.
I think the takeaways would be, not that it’s not occurring, but the opposite, that we do still see it. It doesn’t, at least in this study, appear to be at a higher rate, which was a concern earlier, particularly when you’re looking at studies that were enriched for heavily pretreated, relapsed/refractory CLL patients, and then you see a substantial amount of the progression events are actually Richter’s transformation. That’s kind of skewed by the patient cohort that’s going in; they’ve already seen chemoimmunotherapy, they’ve already seen a number of agents, and they’re far along in their course. But if you see a new patient today in clinic, what does that actual risk or likelihood look like? I think this gives us a little bit better assessment. Certainly longer follow-up and validating in other cohorts will be important. But this gives us some idea that that one, it’s still occurring, and two, does not at least appear to be at a higher rate than in in the prior era.
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