Waldenström's macroglobulinemia: Imbruvica prescribing information updated to include long-term data
The U.S. Food and Drug Administration ( FDA ) has approved the update of the Imbruvica ( Ibrutinib ) Prescribing Information to include efficacy and safety data for the combination of Imbruvica with Rituximab for the treatment of Waldenström's macroglobulinemia ( WM ), based on the final analysis of the phase 3 iNNOVATE study.
First approved in 2013, Imbruvica is currently available to patients with several types of blood cancer, as well as chronic graft-versus-host disease. It was approved as a monotherapy for Waldenström's macroglobulinemia in 2015 and as a combination therapy with Rituximab in 2018 based on the iNNOVATE primary analysis.
As of today, Imbruvica is the only Bruton's tyrosine kinase ( BTK ) inhibitor approved to treat Waldenström's macroglobulinemia.
Waldenström's macroglobulinemia typically affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may also be affected.
In the U.S., there are approximately 2,800 new cases of Waldenström's macroglobulinemia each year.
The Imbruvica Prescribing Information now includes final analysis data, with an overall follow-up of 63 months, from the phase 3 iNNOVATE clinical trial.
With additional follow-up since the primary analysis, the combination of Imbruvica plus Rituximab continued to demonstrate prolonged progression-free survival ( PFS ) in patients with Waldenström's macroglobulinemia compared to Rituximab monotherapy.
Patients treated in the Imbruvica arm experienced a 75% reduction in risk of disease progression or death compared to Rituximab monotherapy ( hazard ratio [ HR ] 0.25; 95% confidence interval [ CI ]: 0.15-0.42; p less than 0.0001 ).
In the iNNOVATE study primary analysis, the most common side effects ( greater than or equal to 20% ) in patients treated with Imbruvica plus Rituximab were bruising, muscle pain, bleeding problems, diarrhea, rash, joint pain, nausea and high blood pressure.
iNNOVATE, randomized, placebo-controlled, double-blind, study, which enrolled 150 patients with relapsed / refractory and treatment-naïve Waldenström's macroglobulinemia.
All patients received intravenous Rituximab 375 mg/m2 once weekly for four consecutive weeks, followed by a second four-weekly Rituximab course following a three-month interval.
Patients were randomized to receive either Ibrutinib 420 mg or placebo once daily continuously until criteria for treatment discontinuation were met.
The primary endpoint was progression-free survival; secondary endpoints included overall response rate; hematological improvement measured by hemoglobin; time-to-next treatment; overall survival; and number of participants with adverse events as a measure of safety and tolerability within each treatment arm. ( Xagena )
Source: Abbvie, 2020