Ibrutinib Treatment in Waldenström Macroglobulinemia: The iNNOVATE Study

Oral presentation by Dr. Christian Buske

In Canada, symptomatic patients with Waldenström’s macroglobulinemia (WM) are treated with a variety of initial regimens including bendamustine with or without rituximab, chlorambucil with or without rituximab, and rituximab alone. Relapsed patients are either re-treated with one of those regimens or occasionally with ibrutinib. However, access to ibrutinib is currently limited.

This iNNOVATE study establishes ibrutinib as one of the most highly effective treatments available for WM, in both the treatment-naïve and relapsed situations, and shows that it is more effective than rituximab as a single agent. The similarity in the response rates and response durability of ibrutinib plus rituximab and ibrutinib alone in arms A and C of the trial implies that most, if not all, of the beneficial impact is due to the ibrutinib alone. Importantly, there were no novel safety signals identified, and ibrutinib was associated with known rates of adverse events and was generally well tolerated.

These data will strengthen the case for the use of ibrutinib for WM, especially in the relapsed setting. Given ibrutinib’s cost, need for long-term treatment, and known toxicities, ibrutinib will generally be seen as a good second-line choice for treatment and more established approaches will continue to be chosen for primary treatment. Therefore, I do believe that ibrutinib will be used with increasing frequency for the management of WM.

In the future, a direct comparison of ibrutinib alone versus standard treatment for previously untreated patients with symptomatic WM should be done and has a good chance of demonstrating that ibrutinib alone should be the primary treatment choice for such patients. Finally, it is striking to see the similarity of these results with those seen with the use of ibrutinib alone or with rituximab in elderly patients with chronic lymphocytic leukemia (abstract 6).

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