Imbruvica plus Rituximab approved by FDA as first chemotherapy-free combination treatment in adults with Waldenström's macroglobulinemia
The U.S. Food and Drug Administration ( FDA ) has approved Imbruvica ( Ibrutinib ) plus Rituximab ( Rituxan ) for the treatment of adult patients with Waldenström's macroglobulinemia ( WM ), a rare and incurable type of non-Hodgkin's lymphoma ( NHL ).
With this approval, Imbruvica prescribing information now includes combination use with Rituximab, representing the first and only chemotherapy-free combination treatment specifically indicated for the disease.
Imbruvica was first approved as a single agent therapy for Waldenström's macroglobulinemia in January 2015.
Ibrutinib is a first-in-class, oral, once-daily therapy that mainly works by blocking a protein called Bruton's tyrosine kinase ( BTK ).
BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells as well as other serious, debilitating conditions.
Ibrutinib blocks signals that tell malignant B cells to multiply and spread uncontrollably.
This new FDA approval is supported by data from the phase 3 iNNOVATE trial evaluating Ibrutinib in combination with Rituximab, versus Rituximab alone, in 150 patients with previously untreated and relapsed / refractory Waldenström's macroglobulinemia.
At a median follow-up of 26.5 months, the study has demonstrated a significant improvement in progression-free survival ( PFS ) with Ibrutinib plus Rituximab compared to Rituximab alone ( 30-month PFS rates were 82% versus 28%, respectively ).
Patients taking Ibrutinib plus Rituximab also experienced an 80% reduction in relative risk of disease progression or death than those only treated with Rituximab ( hazard ratio, HR=0.20; confidence interval: 0.11-0.38, P less than 0.0001 ).
These data were published in The New England Journal of Medicine.
Waldenström's macroglobulinemia is a rare, slow-growing and incurable form of NHL with limited treatment options.
Waldenström's macroglobulinemia typically affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen also may be affected.
In the U.S., there are about 2,800 new cases of Waldenström's macroglobulinemia each year.
The most common adverse reactions ( occurring in 20% or more of patients ) of all grades in patients treated with Ibrutinib plus Rituximab in the iNNOVATE study were bruising ( 37% ), musculoskeletal pain ( 35% ), hemorrhage ( 32% ), diarrhea ( 28% ), rash ( 24% ), arthralgia ( 24% ), nausea ( 21% ), and hypertension ( 20% ).
In combination with Rituximab or as a single agent, the recommended dose of Ibrutinib for adults with Waldenström's macroglobulinemia is 420 mg taken orally once daily until disease progression or unacceptable toxicity.
iNNOVATE enrolled 150 patients with relapsed / refractory and treatment-naïve Waldenström's macroglobulinemia.
Patients were randomized to receive intravenous Rituximab 375 mg/m2 once weekly for four consecutive weeks, followed by a second four-weekly Rituximab course following a three-month interval.
All patients received either Ibrutinib 420 mg or placebo once daily continuously until criteria for permanent discontinuation were met.
The primary endpoint was progression-free survival, with secondary endpoints including 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.
Imbruvica is FDA-approved in six distinct patient populations: chronic lymphocytic leukemia ( CLL ), small lymphocytic lymphoma ( SLL ), Waldenström's macroglobulinemia ( WM ), along with previously-treated mantle cell lymphoma ( MCL ), previously-treated marginal zone lymphoma ( MZL ) and previously-treated chronic graft-versus-host disease ( cGVHD ). ( Xagena )
Source: Abbvie, 2018