Jennifer A. Woyach, MD, on Updated Results of the AO41202 Trial Testing Ibrutinib Regimens in CLL at ASH 2021

Jennifer A. Woyach, MD, spoke about the results of a study conducted in elderly patients treated with an ibrutinib-containing regimen for chronic lymphocytic leukemia at 55 months of follow-up.

During the 2021 American Society of Hematology Annual Meeting, Jennifer A. Woyach, MD, associate professor in the Division of Hematology at The Ohio State University, discussed follow-up results to the phase 3 AO41202 study (NCT01886872), in which single-agent ibrutinib (Imbruvica) or an ibrutinib-containing regimen yielded superior results compared with the bendamustine-plus-rituximab (Rituxan) regimen for patients over the age of 65 years with untreated chronic lymphocytic leukemia.


At the 55-month follow-up, we saw that the results continued to show an advantage for the 2 ibrutinib-containing regimens over bendamustine and rituximab at 48 months. Over three-quarters of patients treated with either ibrutinib or ibrutinib plus rituximab remain progression free, and less than 50% of those treated with bendamustine and rituximab are progression free at that same time.

We see no difference between the 2 ibrutinib-containing regimens showing that rituximab does not add benefit to ibrutinib when given in this manner. We still do not see a difference in overall survival among the 3 treatment arms, which is to be expected as a study has a crossover design, so patients who were enrolled in the bendamustine-and-rituximab arm, once they progress, can cross over to ibrutinib given as a single agent.

When we look at subgroup analyses, we again see that all patient groups really benefit from the ibrutinib regimens compared with bendamustine plus rituximab. We see a greater magnitude of benefit for patients with higher-risk disease, those with 17p deletion, those with complex karyotype, and those with unmethylated ZAP-70 which we use as a surrogate for unmutated immunoglobulin heavy-chain gene variable region somatic hypermutation [IGHV]. Those patients all seem to have the most benefit from ibrutinib versus chemoimmunotherapy. We do see benefits to the ibrutinib regimens across all subgroups.

We also looked at some of the special adverse [effects] that we see with ibrutinib, namely hypertension and atrial fibrillation. As we’ve seen before in some retrospective studies, we do see that patients continue to get atrial fibrillation and continue to get hypertension as they’re treated for long periods of time. With atrial fibrillation, specifically, we have about a 15% incidence of atrial fibrillation at 36 months. This is one toxicity that does appear to be higher in patients who are older than patients were younger.


Woyach JA, Ruppert AS, Heerema NA, et al. Long-term results of Alliance AO41202 show continued advantage of ibrutinib-based regimens compared with bendamustine plus rituximab (BR) chemoimmunotherapy. Presented at: 63rd American Society of Hematology Annual Meeting; December 11-13, 2021; Atlanta, GA. Accessed December 6, 2021.