Ibrutinib Alone or with Rituximab in Untreated Older Patients with CLL

Oral presentation by Dr. Jennifer A. Woyach

In Canada, treatment-naïve symptomatic elderly (age >65 years) patients with chronic lymphocytic leukemia (CLL), but without evidence of deletion 17p (del[17p]), are treated with a variety of initial regimens including bendamustine with or without rituximab, chlorambucil with or without rituximab, or obinutuzumab and rituximab alone.

The Alliance North American Intergroup Study A041202 establishes ibrutinib as the most highly effective treatment available for elderly treatment-naïve patients with CLL and shows that it is more effective than the combination of bendamustine plus rituximab, which is widely seen as the previously most effective treatment for such patients in Canada. The similarity in the response rates and response durability of ibrutinib plus rituximab and ibrutinib alone in arms 2 and 3 of the trial implies that most, if not all, of the beneficial impact is due to the ibrutinib alone. There were no novel safety signals identified. Ibrutinib was associated with known rates of adverse events (AEs) and major AEs for that agent, and it was generally well tolerated.

The data presented here will make a very strong case for the use of ibrutinib alone for elderly patients with symptomatic CLL, especially including those with del(17p), mutation of p53, and other negative prognostic factors. Although I suspect that ibrutinib will be used with increasing frequency in these patients, that decision will be tempered by ibrutinib’s cost, need for long-term treatment, and known, although uncommon, toxicities.

In terms of the future outlook, I believe that there is an urgent need to determine if it is necessary to continue ibrutinib indefinitely or whether equivalent benefit can be achieved with defined duration treatment.

Finally, of note, the similarity of the results presented in this session with those seen with the use of ibrutinib alone or with rituximab in patients with Waldenström’s macroglobulinemia (abstract 149) is striking.

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