Ibrutinib Plus Rituximab for Waldenström Macroglobulinemia: Final Results From the iNNOVATE Trial

Ibrutinib added to rituximab sustained efficacy and significantly reduced risk of disease progression or death over rituximab alone for patients with Waldenström macroglobulinemia (WM) regardless of MYD88 and CXCR4 mutation status or prior treatment, according to final results from the phase 3 iNNOVATE trial.

The double-blind trial enrolled 150 adult patients with confirmed symptomatic WM. Patients were randomized in a 1:1 ratio to oral once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab and were treated until disease progression or unacceptable toxicity.

Participants could have de novo or previously treated disease, but those who received prior rituximab had to have had at least a minor response to their last rituximab-based regimen and could not have received rituximab in the 12 months prior to study initiation.

The primary end point of the trail was progression-free survival (PFS). Secondary end points included response rate, time to next treatment (TTNT), hemoglobin improvement, and overall survival (OS).

After a median follow-up of 50 months, the median PFS in the ibrutinib group was not reached vs 20.3 months in the placebo group (hazard ratio [HR], 0.250; P <.0001). This PFS benefit was maintained regardless of MYD88 and CXCR4 mutation status, receipt of prior treatment, or key patient characteristics.

Over three-quarters (76%) of patients in the ibrutinib group experienced a partial response or better vs 31% in the placebo group (P <.0001). Median TTNT was not reached vs 18 months, respectively. Median OS was not reached in either group.

In addition, 77% of patients in the  ibrutinib group had sustained hemoglobin improvement vs 43% of patients in the placebo group (P <.0001).

Source:

Buske C, Tedeschi A, Trotman J, et al. Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study. J Clin Oncol. Published online October 4, 2021. doi:10.1200/JCO.21.00838