During the 2021 American Society of Hematology annual meeting, Jennifer A. Woyach, MD, associate professor in the division of hematology at Ohio State University, discussed the follow-up results of the phase 3 study AO41202 (NCT01886872), in which a single agent ibrutinib (Imbruvica) or a regimen containing ibrutinib showed superior results compared to the bendamustine-plus-rituximab (Rituxan) regimen in patients over 65 years of age with of untreated chronic lymphocytic leukemia.
At the 55-month follow-up, we saw that the results continued to show an advantage for the 2 treatment regimens containing ibrutinib over bendamustine and rituximab at 48 months. More than three quarters of patients treated with ibrutinib or ibrutinib plus rituximab have no progression, and less than 50% of those treated with bendamustine and rituximab have no progression at the same time.
We do not see any difference between the 2 treatment regimens containing ibrutinib, which shows that rituximab does not add benefit to ibrutinib when administered in this way. We still do not see a difference in overall survival between the 3 treatment arms, which is normal as one study has a crossover design, so patients who were enrolled in the bendamustine-and-rituximab arm, once they progress, can cross with ibrutinib given as monotherapy.
When we look at the subgroup analyzes, we again find that all patient groups actually benefited from ibrutinib regimens compared to bendamustine plus rituximab. We see greater magnitude of benefit for patients with high-risk disease, those with a 17p deletion, those with a complex karyotype, and those with unmethylated ZAP-70 which we use as a surrogate for somatic hypermutation of the variable region of the unmutated immunoglobulin heavy chain gene [IGHV]. These patients all seem to get the most benefit from ibrutinib compared to chemoimmunotherapy. We see benefits for ibrutinib regimens in all subgroups.
We also looked at some of the specific side effects [effects] seen with ibrutinib, namely hypertension and atrial fibrillation. As we have seen before in some retrospective studies, we find that patients continue to experience atrial fibrillation and continue to have hypertension when treated for long periods of time. With atrial fibrillation in particular, we have about a 15% incidence of atrial fibrillation at 36 months. This is a toxicity which appears to be higher in older patients than in younger patients.
Woyach JA, Ruppert AS, Heerema NA, et al. Long-term results from Alliance AO41202 show a continued advantage of ibrutinib-based regimens over bendamustine plus rituximab (BR) chemoimmunotherapy. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-13, 2021; Atlanta, Georgia. Accessed December 6, 2021. https://bit.ly/31EcBlO