William G. Wierda, MD, PhD, on CLL/SLL: Updated Findings on Ibrutinib and Venetoclax

This year I presented an update of the CAPTIVATE study, which is a multi-center study, an international study, actually, of a combined targeted therapy for patients with chronic lymphocytic leukemia who were previously untreated. The treatment was for three months of ibrutinib monotherapy, followed by 12 months or 12 cycles of combined therapy, ibrutinib plus venetoclax. There were two cohorts in this study. We focused, in this presentation, on the fixed-duration cohort. So all the patients received the 12 cycles of combined therapy and then stopped treatment for follow-up. And this was a five-and-a-half-year update of these data. We've presented these data previously with earlier data cuts, but the overall summary of and important points that were presented at ASCO this year was we focused on patients with high-risk features. Those were patients who had 17p deletion or mutated TP53 or a complex karyotype. And we reported the outcomes for that subgroup of patients compared to individuals who didn't have those high-risk features. We saw a lower five-year progression-free survival rate for patients with high-risk features. We also saw a lower five-year progression-free survival rate for patients with an unmutated immunoglobulin gene compared to those who have a mutated immunoglobulin gene. But overall, we did not identify, or we could not estimate, the median progression-free survival for the whole group or for the subgroups. So these patients are doing exceptionally well with a median that extends beyond a five-year follow-up, which illustrates to us that it is a reasonable option to recommend for patients, even with a high-risk feature, this fixed duration treatment with combined targeted therapy. Again, this is an all-oral regimen. It did not include a CD20 antibody, and we saw very high undetectable MRD rates, which correlated with long progression-free survival. This trial, again, has been previously presented. This was a follow-up and longer follow-up data available. It has been an important regimen. It is approved in the European Union. It's not approved in the U.S., but we do have it on the NCCN guidelines. So it is a treatment option for our patients. One of the questions has been what is the optimal patient population for this regimen? My opinion is that patients who do very well with this regimen are patients who have an unmutated immunoglobulin gene, their MRD rates, undetectable MRD rate, is higher than patients with a mutated immunoglobulin gene, and it's a very well-tolerated combination for our patients. And so I think of this regimen when I have a patient who is younger than 70 and has an unmutated immunoglobulin gene as an ideal first-line treatment option for that patient population.